Serum Elafin Levels in Patients with IgA Vasculitis: A Prospective Case-Control Study

Serum Elafin Levels in Patients with IgA Vasculitis: A Prospective Case-Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Serum Elafin Levels in Patients with IgA Vasculitis: A Prospective Case-Control Study Cengiz Zeybek, Ahmet Bolat, Bedriye Nuray Alpman, Tuğba İpek Karaoğlu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6700136/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Pediatric Rheumatology → Version 1 posted 9 You are reading this latest preprint version Abstract Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis characterized by perivascular IgA deposition and neutrophil activation. Elafin, an anti-inflammatory and anti-protease protein expressed by epithelial and select immune cells, may play a role in modulating vascular inflammation. We evaluated serum elafin levels in pediatric patients with IgAV during active stage and remission, and investigated their associations with disease activity, organ involvement, and systemic inflammatory markers. Methods This single-center prospective case-control study included 51 pediatric patients diagnosed with IgAV and 54 age- and sex-matched healthy controls. Paired data were obtained from the same IgAV patients during the remission phase, allowing intra-individual comparisons. Serum elafin levels were quantified using enzyme-linked immunosorbent assay (ELISA). Inflammatory parameters, including complete blood counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were assessed in all participants. Results Serum elafin levels were significantly elevated in patients with IgAV (45.43 ± 11.11 ng/dL; range: 34.02–69.28) compared to healthy controls (27.44 ± 12.66 ng/dL; range: 0.01–41.84) (p < 0.001), with the highest concentrations observed during active disease stage (p < 0.001). Patients with visceral involvement (gastrointestinal, renal, or scrotal) exhibited significantly higher elafin levels (p < 0.05), whereas no significant association was found with isolated skin or joint involvement. Serum elafin levels demonstrated positive correlations with the ESR (p = 0.001, r = 0.418), CRP (p < 0.001, r = 0.547), neutrophil-to-lymphocyte ratio (p = 0.002, r = 0.355), and systemic immune-inflammation index (p = 0.003, r = 0.347). Receiver operating characteristic curve analysis identified an optimal serum elafin cut-off value of 35.38 ng/dL for distinguishing active IgAV, yielding a sensitivity of 86.2% and specificity of 77.8%. Conclusion Serum elafin levels were significantly elevated during the active stage of IgAV and may serve as a potential biomarker for disease activity, particularly in patients with visceral involvement. Children IgA vasculitis Elafin Biomarker Inflammation Figures Figure 1 Figure 2 Introduction Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common type of vasculitis in children; it is characterized by the deposition of immunoglobulin A1 (IgA1)-dominant immune complexes in the walls of small vessels. Beyond its hallmark cutaneous manifestations—namely, palpable purpura typically confined to the lower extremities—IgAV can affect the gastrointestinal (GI) tract, joints, and kidneys [ 1 ]. A critical step in the pathogenesis of IgAV involves the production of galactose-deficient IgA1 (Gd-IgA1), which, in response to a presumed infectious trigger, forms circulating immune complexes with anti-Gd-IgA1 autoantibodies; subsequently, these complexes are deposited in target tissues and activate inflammatory pathways [ 2 ]. Elafin and its precursor, trappin-2, along with secretory leukocyte peptidase inhibitor, are potent endogenous serine protease inhibitors and members of the chelonianin family [ 3 ]. Elafin exhibits a relatively narrow inhibitory profile, selectively targeting neutrophil elastase (NE), proteinase-3, pancreatic elastase and endogenous vascular elastase [ 4 ]. In vitro studies have demonstrated that elafin expression is upregulated in response to proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in various cell lines [ 5 , 6 ]. By inhibiting NE, elafin helps mitigate excessive inflammatory responses, preventing tissue and organ damage and contributing to maintenance of a controlled and physiologically appropriate inflammatory process [ 7 ]. Beyond its anti-protease activity, elafin exerts anti-inflammatory effects by suppressing lipopolysaccharide (LPS) and lipoteichoic acid-stimulated nuclear factor-kappaB (NF-kappaB) activation in monocytes, resulting in reduced expression of proinflammatory cytokines [ 8 ]. Previous studies have reported higher levels of serum elafin in patients with Behçet's disease, a systemic vasculitic disorder, compared to healthy controls [ 9 ]. Neutrophils and lymphocytes are key immune system cellular components that plays critical roles in inflammation and the pathogenesis of IgAV [ 10 ]. During IgAV, immune complexes contribute to disease pathogenesis by inducing NETosis via activation of FcγRIIIB or CD89 receptors [ 11 , 12 ]. NETosis is a recently characterized mechanism by which neutrophils eliminate pathogens through the release of neutrophil extracellular traps (NETs) [ 13 , 14 ]. In IgAV, elevated levels of NETs and reactive oxygen species have been observed in superficial and deep dermal perivascular tissues [ 15 ]. NET levels increase significantly during the active stage of IgAV and gradually decrease during remission, with NE identified as one of the key NET-associated components [ 16 ]. NE has been implicated in the regulation of elafin expression and secretion, modulating the inflammatory response [ 17 ]. In addition, proinflammatory cytokines, such as IL-1β and TNF-α, play pivotal roles in the initiation and progression of vasculitis [ 18 ]. We hypothesized that serum elafin levels may be altered in IgAV and potentially associated with disease activity and organ involvement. In addition to measuring serum elafin levels, we evaluated and compared inflammation-related parameters derived from the complete blood count (CBC), including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), between the patient and control groups. We investigated potential correlations between these parameters and serum elafin levels. To our knowledge, this is the first study to report serum elafin levels in patients with IgAV. Methods Study design and Patient Selection This single-center, prospective case–control study included 51 children aged < 18 years diagnosed with IgAV and 54 age- and sex-matched healthy controls. Participants were recruited from the pediatric rheumatology outpatient clinic of our hospital between 15 April 2024 and 15 April 2025. IgAV was diagnosed based on the Ankara 2008 criteria, which have been validated by the European League Against Rheumatism, the Pediatric Rheumatology International Trials Organization, and the Pediatric Rheumatology European Society [ 19 , 20 ]. The control group consisted of healthy children of comparable age and sex who presented for routine follow-up examinations. These individuals had normal blood and urine test results and no history or clinical evidence of vasculitis or other chronic organ disorders, and they were not receiving any medication at the time of enrollment. Patients aged ≥ 18 years who had received nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or other immunosuppressive agents for IgAV or its complications within the past 2 weeks, or had evidence of renal dysfunction (glomerular filtration rate 3 x the upper reference limit) were excluded. Patients with chronic conditions, such as congenital heart disease, diabetes mellitus, autoimmune disorders, and hematological disease, a body mass index > 30 kg/m 2 , acute infection, or current medication use were also excluded. Serum elafin levels and inflammation parameters derived from the CBC of patients with active stage IgAV (active IgAV group) were compared with those obtained during remission (inactive IgAV group) and with those of age- and sex-matched healthy controls (control group). The Gülhane Medical Faculty Review Board and Ethics Committee approved the study protocol. The study was performed in accordance with the Declaration of Helsinki (2024/66). Written and oral informed consent was obtained from the study paticipants. Definitions and Data Collection GI involvement was defined as severe abdominal pain with or without clinical indicators of GI bleeding, such as positive fecal occult blood, melena, or hematochezia. Renal involvement was defined as the presence of hematuria (> 5 red blood cells per high-power field in a centrifuged urine specimen) and non-nephrotic proteinuria (spot urine protein/creatinine ratio > 0.2 or 4–40 mg/m 2 /h), or nephrotic syndrome (spot urine protein/creatinine ratio > 2 or > 40 mg/m 2 /h). Scrotal involvement was defined as the presence of epididymitis, orchitis, or testicular hematoma, or testicular torsion identified on ultrasound, accompanied by scrotal and testicular pain and edema. Ultrasound confirmation was performed in all patients presenting with scrotal symptoms. GI, renal, and scrotal involvement were collectively classified as visceral involvement [ 21 ]. The active stage was defined as the initial phase of the disease, characterized by new-onset symptoms, whereas the inactive (remission) stage was defined by the absence of clinical signs and laboratory findings associated with disease activity [ 22 ]. Following a 12-h fast, peripheral blood samples were collected from antecubital vein of all participants to assess serum elafin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CBC parameters. In the study group, particular attention was paid to obtaining blood samples during the active stage before the initiation of NSAID and/or corticosteroid therapy, and ≥ 2 weeks after discontinuation of such treatments during the inactive stage. Collected blood samples were kept at room temperature for 30 min, then centrifuged at 3,500 rpm for 10 min to obtain serum for elafin and CRP analysis. Serum samples were stored at -80°C until the elafin quantification. CRP and the ESR were analyzed on the same day the blood samples were collected. Serum elafin concentrations were determined using an enzyme-linked immunosorbent assay (catalogue number: E4762Hu; Bioassay Technology Laboratory, Shanghai, China), with a reported sensitivity of 0.5 ng/dL. The ESR was assessed using the Westergren method, and CRP levels were measured using an automated analyzer (AU680®; Beckman Coulter, Miami, FL, USA), with reference ranges of 0–20 mm/h fort he ESR and 0–5 mg/dL fort he CRP. CBC parameters were measured using an automated hematology analyzer (Beckman Coulter). Derived CBC-based inflammatory indices included the NLR, MLR, PLR and SII. The SII was calculated using the following formula: neutrophil count (K/uL) X platelet count (K/uL) / lymphocyte count (K/uL). The NLR was calculated by dividing the neutrophil count by the lymphocyte count; the PLR by dividing the platelet count by the lymphocyte count; and the MLR by dividing the monocyte count by the lymphocyte count. Statistical Analysis Statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Quantitative variables are presented as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables were compared using the chi-square test. The Shapiro–Wilk test was used to assess the normality of the data distribution. For comparisons between two independent groups, the independent-samples t-test was used for normally distributed variables, whereas the Mann–Whitney U test was used for non-normally distributed variables. Paired (dependent) samples were analyzed using the Wilcoxon signed-rank test. Correlations between variables were evaluated using Spearman's rank correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for elafin, as well as its sensitivity and specificity for diagnosing IgAV. P -values < 0.05 were considered statistically significant. Results Blood samples from 51 children diagnosed with IgAV during active and inactive stages were compared with those from 54 age- and sex-matched healthy controls. The mean age of the participants in the IgAV and control groups was 8.45 ± 3.27 and 8.85 ± 3.84 years, respectively, with no statistically significant difference ( p = 0.57). The IgAV group comprised 35 males (68.6%), whereas the control group included 31 males (57.4%; p = 0.23) (Table 1 ). Serum elafin levels were significantly higher in children with active IgAV (45.43 ± 11.11 ng/dL; range: 34.02–69.28 ng/dL) compared to the control group (27.44 ± 12.66 ng/dL; range: 0.01–41.84 ng/dL) ( p < 0.001). In addition, leukocyte count, neutrophil count, NLR, SII, ESR, and CRP levels were significantly higher in children with active IgAV compared to healthy controls ( p = 0.005, 0.007, 0.006, 0.007, < 0.001, and < 0.001, respectively) (Table 1 ) Table 1 Demographic characteristics and laboratory parameters of patients with IgAV and healthy controls Parameters Active IgAV (n = 51) Control (n = 54) p Age (years) 8.45 ± 3.27 8.85 ± 3.84 0.57* F/M (n, %) 16 (31.4)/35 (68.6) 23 (42.6)/31 (57.4) 0.23 † Hemoglobin (g/dL) 13.12 ± 1.12 13.43 ± 1.32 0.30* Thrombocyte (10 3 /µl) 366111.11 ± 122111.95 308402.22 ± 102474.74 0.08 § Leukocyte (10 3 /µl) 9755.15 ± 3700.43 7624.88 ± 248.48 0.005* Neutrophil (10 3 /µl) 6261.85 ± 648.81 4284.44 ± 317.29 0.007 § Lymphocyte (10 3 /µl) 2683.71 ± 219.31 2744.88 ± 114.99 0.29 § Monocyte (10 3 /µl) 574.44 ± 52.21 492.66 ± 21.82 0.16 § NLR 2.65 ± 1.98 1.67 ± 0.97 0.006 § PLR 151.34 ± 70.17 125.92 ± 40.06 0.054 § MLR 0.23 ± 0.14 0.21 ± 0.20 0.76 § SII 973.41 ± 828.85 566.61 ± 415.85 0.007 § Elafin (ng/dL) 45.43 ± 11.11 27.44 ± 12.66 < 0.001 § ESR (mm/h) 15.33 ± 10.97 6.51 ± 5.05 < 0.001 § CRP (mg/dL) 12.17 ± 12.03 2.09 ± 2.01 < 0.001 § Data are given with mean ± standard deviation F,female; M,male; IgAV, IgA vasculitis; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; *Student t-test † Chi-Square test; § Mann–Whitney U test A statistically significant difference in serum elafin levels was observed between patients with active and inactive IgAV. Elafin levels were significantly higher in the active stage (mean: 45.43 ± 11.11 ng/dL; median: 43.48 ng/dL; range: 34.02–69.28 ng/dL) compared to the inactive stage (mean: 29.31 ± 11.27 ng/dL; median: 31.84 ng/dL; range: 11.54–43.18 ng/dL) ( p < 0.001). Similarly, the ESR, CRP levels, NLR, and SII levels were significantly higher in patients with active IgAV compared to those with inactive IgAV ( p = 0.008, < 0.001, 0.006, and 0.035, respectively), with the highest levels observed in active IgAV group and the lowest in the healthy controls. However, no statistically significant differences were observed between the inactive IgAV group and healthy controls in these parameters (p > 0.05). In addition, no significant differences were observed in the PLR or MLR among the active IgAV, inactive IgAV, and control groups ( p > 0.05; Table 2 ). Table 2 Laboratory measurements in active IgAV, inactive IgAV and control groups Parameters Active IgAV Inactive IgAV Control p (active-control) p (inactive-control) p (active-inacvtive) Elafin (ng/dL) 45.43 ± 11.11 43.48 (13.36) 29.31 ± 11.27 31.84 (6.81) 27.44 ± 12.66 31.50 (5.82) < 0.001 § 0.65 § < 0.001 * ESR (mm/h) 15.33 ± 10.97 12 (15) 7.06 ± 5.19 5 (4.5) 6.51 ± 5.05 5 (3.5) < 0.001 § 0.6 § 0.008 * CRP (mg/dL) 12.17 ± 12.03 5.2 (8.7) 2.49 ± 2.29 1.6 (1.3) 2.09 ± 2.01 1.1 (1.1) < 0.001 § 0.098 § < 0.001 * NLR 2.65 ± 1.98 1.97 (1.2) 1.79 ± 0.61 1.67 (0.87) 1.67 ± 0.97 1.4 (0.85) 0.006 § 0.065 § 0.006 * PLR 151.34 ± 70.17 123.68 (83.96) 127.47 ± 35.54 120.36 (55.53) 125.92 ± 40.06 117.08 (56.83) 0.054 § 0.73 § 0.11 * MLR 0.23 ± 0.14 0.21 (0.12) 0.22 ± 0.15 0.18 (0.08) 0.21 ± 0.20 0.17 (0.10) 0.76 § 0.81 § 0.89 * SII 973.41 ± 828.85 638.22(437.76) 635.43 ± 377.33 494.81 (373) 566.61 ± 415.85 477.71(284.86) 0.007 § 0.42 § 0.035 * Data are given with mean ± standard deviation and median (interquartile range) IgAV, IgA vasculitis; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index § Mann–Whitney U test; *Wilcoxon test Serum elafin levels, as presented in Table 2 , were subjected to pairwise comparisons among the study groups, and the results were visualized using a box plot (Fig. 1 ). Table 3 summarizes the association between serum elafin levels and specific organ involvement in IgAV patients. No statistically significant differences in serum elafin levels were observed between patients with and without skin or joint involvement ( p = 0.56 and p = 0.061, respectively). In contrast, patients with GI, renal, or scrotal involvement exhibited significantly higher serum elafin levels compared to those without these manifestations ( p = 0.033, p = 0.028 and p = 0.022, respectively) (Table 3 ). Table 3 Clinical manifestations in patients with active IgAV and their association with serum elafin levels Parameters Presence Elafin (ng/dL) p Only skin involvement Yes n:20 No n:31 41.77 ± 4.96 43.48 (9.26) 47.26 ± 12.91 42.89 (25.73) 0.56 § Joint involvement Yes n:13 No n:38 41.36 ± 9.25 37.02 (32.44) 49.21 ± 11.66 46.19 (35.26) 0.061 § GIS involvement Yes n:15 No n:36 58.91 ± 14.63 62.65 (24.96) 43.43 ± 9.41 40.17 (10.69) 0.033 § Kidney involvement Yes n:6 No n:45 59.16 ± 9.81 59.25 (13.88) 41.33 ± 10.62 40.05 (11.44) 0.028 § Scrotal involvement Yes n:3 No n:48 61.83 ± 9.34 64.87 44.51 ± 10.23 41.76 (12.24) 0.022 § Data are given with mean ± standard deviation and median (interquartile range) GIS, gastrointestinal system § Mann–Whitney U test No statistically significant correlations were observed between serum elafin levels and the PLR or MLR (r = 0.036, p = 0.76; and r = 0.045, p = 0.741, respectively). Conversely, serum elafin levels demonstrated a moderate positive correlation with ESR (r = 0.418, p = 0.001) and CRP (r = 0.547, p < 0.001). In addition, weak positive correlations were observed between serum elafin levels and the NLR (r = 0.355, p = 0.002) and the SII (r = 0.347, p = 0.003) (Table 4 ) Table 4 Correlation between serum elafin levels and inflammatory parameters Variable Elafin r p ESR 0.418 0.001 CRP 0.547 < 0.001 NLR 0.355 0.002 PLR 0.036 0.76 MLR 0.045 0.741 SII 0.347 0.003 ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index. r: Spearman’s correlation coefficient. ROC curve analysis for the diagnosis of IgAV identified an optimal serum cut-off value of 35.38 ng/dL. At this threshold, serum elafin exhibited a sensitivity of 86.2% and a specificity of 77.8%, with a positive predictive value (PPV) of 17.34% and a negative predictive value (NPV) of 89.64% (Fig. 2 ). Cut off: 35.88 ng/dL Sensitivity: 86.2% Specificity: 77.8% PPV: 17.34% NPV: 89.64% AUC: 0.924 PPV, positive predictive value; NPV, negative predictive value; AUC, area under curve Discussion We evaluated serum elafin levels in patients with IgAV during active and inactive disease stages, comparing these levels with those of healthy controls. Our findings revealed that serum elafin levels were significantly higher during the active stage of IgAV compared to the inactive stage and healthy controls, indicating a potential role of elafin as a biomarker for disease activity. Elafin modulates inflammation and innate immüne responses by inhibiting key transcription factors, such as activator protein-1 and NF-kappaB. This regulatory effect is mediated through suppression of the ubiquitin-proteasome pathway and upregulation of the NF-kappaB inhibitor, IkappaBalpha [ 8 , 23 , 24 ]. However, the precise mechanisms underlying this inhibitory pathways remain uncertain [ 3 ]. In mouse models of LPS-induced inflammation, elafin has accelerated resolution by enhancing neutrophil apoptosis via NF-kappaB modulation; this pro-resolving effect may be attributed to the inhibition of NE and possibly the preservation of intact annexin-1 [ 25 ]. Furthermore, elafin may prevent NE-mediated cleavage of dendritic cell receptors, such as CD40, CD80 and CD86, facilitating apoptotic cell clearance and the resolution of inflammation [ 26 ]. In mouse models of colitis, elafin-expressing mice demonstrated reduced inflammatory cell infiltration, attenuated tissue damage, and suppression of pro-inflammatory cytokines, such as IL-16 and 17, and chemokines [ 27 ]. In addition, the anti-inflammatory effects of elafin may involve increased secretion of IL-10 and decreased secretion of IL-8 via NF-kappaB inhibition [ 23 , 28 , 29 ]. In normal skin samples, no elafin immunoreactivity was observed in the vascular walls. In contrast, elafin immunoreactivity was demonstrated in the endothelial cells of small vessels in the superficial dermis and in intravascular fibrin deposits; these findings suggest a potential role for elafin in fibrin stabilization during vascular injury [ 30 , 31 ]. Similar patterns of elafin expression have been reported in other vasculitides, including microscopic polyangiitis and giant cell arteritis [ 30 ]. Notably, elafin immunoreactivity was not observed in Churg-Strauss syndrome, a condition characterized by predominant eosinophilic rather than neutrophilic infiltration, reinforcing the association between neutrophil activity and elafin expression [ 30 ]. Neutrophil infiltration and the release of NE at sites of vascular injury may initiate a self-perpetuating cycle of tissue damage. NE degrades elastin, and the resulting elastin-derived peptides can attract additional neutrophils, exacerbating inflammation and injury [ 30 ]. Elafin interrupts this destructive feedback loop by inhibiting NE activity and reducing elastin-induced neutrophil chemotaxis [ 32 ]. Elafin is upregulated at sites of inflammation and may play a role in modulating the inflammatory response [ 4 , 33 ]. For instance, elevated serum elafin levels have been positively correlated with disease activity in inflammatory bowel disorder, and elafin has been proposed as a potential biomarker in ulcerative colitis [ 34 ]. In Behçet's disease, another vasculitis, serum elafin levels were significantly higher during the active disease stage compared to healthy controls, with particularly significant elevations in patients presenting with arthritis, suggesting its potential utility as a disease activity marker in this subgroup [ 9 ]. Consistent with these findings, our findings support the notion that elafin may serve as a biomarker reflecting disease activity in IgAV. Despite its high sensitivity, elafin exhibited a low PPV (17.34%) in our study, indicating that elevated serum elafin levels may be observed in a variety of inflammatory conditions beyond IgAV. Conversely, the NPV (89.64%) indicates that low serum elafin levels may be useful in excluding active IgAV, supporting its potential role as a negative biomarker in clinical practice. The administration of elafine via intravenous, intranasal, or aerosolized routes has been demonstrated to be safe and potentially protective in various cardiovascular or pulmonary disorders [ 35 ]. For instance, in murine models, recombinant human elafin mitigates bronchopulmonary dysplasia by inhibition apoptosis and suppressing the release of inflammatory cytokines, primarily via the modulation of NF-kappaB activity [ 36 ]. Phase 1 and 2 clinical trails of intravenous elafin have confirmed its safety profile, with no reported drug-related adverse effects [ 3 ]. Our findings suggest a potential role for elafin in the pathogenesis of vasculitis and raise the possibility that supraphysiologic doses or variants of elafin may hold therapeutic potential in the future [ 3 , 7 , 35 , 37 ]. CBC-derived parameters are considered rapid, simple, and cost-effective indicators of systemic inflammation and immune response. Among these, the SII, NLR, MLR, and PLR are commonly used indices derived from standart CBC results. Considering their capacity to reflect inflammatory status, these ratios are increasingly used as surrogate markers of inflammatory burden in various disease states. For instance, the SII has been demonstrated to be a reliable marker for assessing disease severity in anti-neutrophil cytoplasmic antibody-associated vasculitis and Behçet's disease, as well as for predicting mortality in COVID-19 [ 38 – 40 ]. We observed elevated ESR, CRP levels, and NLR in patients with active IgAV, consistent with prior studies [ 41 , 42 ]. Furthermore, serum elafin levels were positively correlated with the ESR, CRP, NLR, and SII, reinforcing its potential as an inflammatory marker. Although limited studies have evaluated the SII in IgAV, Güngörer et al. [ 43 ] reported that SII is a valuable parameter for detecting visceral involvement, and Öksel et al. [ 44 ] identified the SII as a predictor of GI complications. Although these previous studies focused on internal comparisons within IgAV cohorts, our study demonstrated a significantly higher SII in patients with active IgAV compared to healthy controls. Consistent with prior study, we observed elevated SII value in IgAV patients with visceral involvement [ 43 ]. Among systemic inflammatory markers, the SII is considered a more objective and comprehensive indicator of the balance between pro-inflammatory and immune responses than the PLR, NLR, or MLR [ 45 ]. Our study has several strengths. First, to our knowledge, this is the first study to evaluate serum elafin levels in pediatric patients with IgAV. Second, the intra-individual comparison between active and inactive disease stages allows for a more precise assessment of disease-related changes, minimizing inter-individual variability. Third, blood samples were collected before the administration of immunosuppressive therapies, eliminating potential confounding effects of medications, particularly corticosteroids [ 46 , 47 ]. However, our study has several limitations. The relatively small sample size may limit the generalizability of the findings. Moreover, patients with less common organ involvement, such as the central nervous system or the urogenital tract involvement such as the ureter, were not represented in the cohort, precluding analysis of elafin expression in these manifestations. Conclusions Our findings suggest that serum elafin levels are significantly elevated in children with active IgAV compared to those in remission and healthy controls. Elafin may serve as a valuable biomarker for disease activity and visceral involvement in IgAV. Moreover elafin could play a mechanistic role in disease pathogenesis by modulating inflammation and vascular injury. Further larger multicenter studies are needed to elucidate the role of elafin across diverse clinical phenotypes of IgAV and to evaluate the therapeutic potential of elafin and its variants in vasculitic disorders. Abbreviations IgAV Immunoglobulin A Vasculitis IgA1 Immunoglobulin A1 CRP C-reactive protein ESR Erythrocyte Sedimentation Rate GI Gastrointestinal Gd-IgA1 Galaktose-deficient IgA1 NE Neutrophil elastase IL Interleukine TNF Tumour Necrosis Factor LPS Lipopolysaccharide NF-kappaB Nuclear factor-kappaB CD Cluster of differentiation NETs Neutrophil ekstraselular traps NLR Neutrophil-to-lymphocyte ratio MLR Monocyte-to-lymphocyte ratio SII Systemic immune-inflammation CBC Complete Blood Count NSAID Nonsteroidal anti-inflammatory drug SD Standart deviation ROC Receiver operating characteristic F Female M Male GIS Gastrointestinal system PPV Positive predictive value NPV Negative predictive value AUC Area under curve COVID Coronavirus disease Declarations Acknowledgements I am extremely thankful to Dr. Çiğdem YÜCEL for help in ELISA studies. Author contributions Came up with the study’s concept and design: C.Z., A.B., VG; The data collection was carried out: C.Z., B.N.A., N.Ö., V.G.; Were responsible for analyzing and interpreting the results: C.Z., A.B., V.G.; The initial draft of the paper was prepared: C.Z., A.B., V.G.; The ethics committee approval process: C.Z., T.İ.K.;,The results were evaluated by all authors, who then approved the final version of this manuscript Funding As far as funding is concerned, the authors did not get any financial assistance for research and/or authorship of this article. Data availability The dataset used/analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was approved by the Gülhane Medical Faculty Review Board and Ethics Committee and conducted to the principles of the Helsinki Declaration (2024/66). Written and oral informed consent was collected for all subjects. The study was approved by the Institutional Ethics Committee prior to study Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Yalçındag A, Sundel R. Vasculitis in childhood. Curr Opin Rheumatol. 2002;13:422–7. Song Y, Huang X, Yu G, Qiao J, Cheng J, Wu J, et al. Pathogenesis of IgA vasculitis: An up-to-date review. Front Immunol. 2021;12:771619. Deraison C, Bonnart C, Langella P, Roget K, Vergnolle N. Elafin and its precursor trappin-2: What is their therapeutic potential for intestinal diseases? Br J Pharmacol. 2023;180:144–60. Moreau T, Baranger K, Dadé S, Dallet-Choisy S, Guyot N, Zani ML. Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family. Biochimie. 2008;90:284–95. Tanaka K, Fujioka A, Tajima S, Ishibashi A, Hirose S. 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Barut K, Sahin S, Kasapcopur O. Pediatric vasculitis. Curr Opin Rheumatol. 2016;28:29–38. Behnen M, Leschczyk C, Möller S, Batel T, Klinger M, Solbach W, et al. Immobilized immune complexes induce neutrophil extracellular trap release by human neutrophil granulocytes via FcgammaRIIIB and Mac-1. J Immunol. 2014;193:1954–65. Aleyd E, Al M, Tuk CW, van der Laken CJ, van Egmond M. IgA complexes in plasma and synovial fluid of patients with rheumatoid arthritis induce neutrophil extracellular traps via FcαRI. J Immunol. 2016;197:4552–9. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5. Guimarães-Costa AB, Nascimento MT, Froment GS, Soares RP, Morgado FN, Conceição-Silva F, et al. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proc Natl Acad Sci U S A. 2009;106:6748–53. Bergqvist C, Safi R, El Hasbani G, Abbas O, Kibbi A, Nassar D. Neutrophil extracellular traps are present in immune-complex-mediated cutaneous small vessel vasculitis and correlate with the production of reactive oxygen species and the severity of vessel damage. Acta Derm Venereol. 2020;100:adv00281. Chen XQ, Tu L, Zou JS, Zhu SQ, Zhao YJ, Qin YH. The involvement of neutrophil extracellular traps in disease activity associated with IgA vasculitis. Front Immunol. 2021;12:668974. Reid PT, Marsden ME, Cunningham GA, Haslett C, Sallenave JM. Human neutrophil elastase regulates the expression and secretion of elafin (elastase-specific inhibitor) in type II alveolar epithelial cells. FEBS Lett. 1999;457:33–7. Nowack R, Flores-Suárez LF, van der Woude FJ. New developments in pathogenesis of systemic vasculitis. Curr Opin Rheumatol. 1998;10:3–11. Prais D, Amir J, Nussinovitch M. Recurrent Henoch-Schonlein purpura in children. J Clin Rheumatol. 2007;13:25–8. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798–806. Du L, Wang P, Liu C, Li S, Yue S, Yang Y. Multisystemic manifestations of IgA vasculitis. Clin Rheumatol. 2021;40:43–52. Ece A, Kelekçi S, Kocamaz H, Hekimoğlu A, Balik H, Yolbaş I, et al. Antioxidant enzyme activities, lipid peroxidation, and total antioxidant status in children with Henoch-Schönlein purpura. Clin Rheumatol. 2008;27:163–9. Henriksen PA, Hitt M, Xing Z, Wang J, Haslett C, Riemersma RA, et al. Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappa B-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. J Immunol. 2004;172:4535–44. Sallenave JM, Cunningham GA, James RM, McLachlan G, Haslett C. Regulation of pulmonary and systemic bacterial lipopolysaccharide responses in transgenic mice expressing human elafin. Infect Immun. 2003;71:3766–74. Vago JP, Tavares LP, Sugimoto MA, Lima GL, Galvão I, de Caux TR, et al. Proresolving actions of synthetic and natural protease inhibitors are mediated by annexin A1. J Immunol. 2016;196:1922–32. Roghanian A, Drost EM, MacNee W, Howie SE, Sallenave JM. Inflammatory lung secretions inhibit dendritic cell maturation and function via neutrophil elastase. Am J Respir Crit Care Med. 2006;174:1189–98. Motta JP, Magne L, Descamps D, Rolland C, Squarzoni-Dale C, Rousset P, et al. Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis. Gastroenterology. 2011;140:1272–82. Roussilhon C, Bang G, Bastaert F, Solhonne B, Garcia-Verdugo I, Peronet R, et al. The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria. Sci Rep. 2017;7:42243. Safavi F, Rostami A. Role of serine proteases in inflammation: Bowman-Birk protease inhibitor (BBI) as a potential therapy for autoimmune diseases. Exp Mol Pathol. 2012;93:428–33. Muto J, Fujimoto N, Ono K, Kobayashi T, Chen KR, Suzuki S, Wachi H, et al. Deposition of elafin in the involved vascular wall of neutrophil-mediated cutaneous vasculitis. J Eur Acad Dermatol Venereol. 2016;30:1544–9. Guyot N, Zani ML, Maurel MC, Dallet-Choisy S, Moreau T. Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases when they are covalently bound to extracellular matrix proteins by tissue transglutaminase. Biochemistry. 2005;44:15610–8. Zaidi SH, You XM, Ciura S, O'Blenes S, Husain M, Rabinovitch M. Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice. J Clin Invest. 2000;105:1687–95. Sallenave JM. Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity. Am J Respir Cell Mol Biol. 2010;42:635–43. Krawiec P, Pac-Kożuchowska E. Clinical significance of serum elafin in children with inflammatory bowel disease. Biomedicines. 2022;10:3267. Shaw L, Wiedow O. Therapeutic potential of human elafin. Biochem Soc Trans. 2011;39:1450–4. Li K, Zhang F, Wei L, Han Z, Liu X, Pan Y, et al. Recombinant human elafin ameliorates chronic hyperoxia-induced lung injury by inhibiting nuclear factor-kappa B signaling in neonatal mice. J Interferon Cytokine Res. 2020;40:320–30. Small DM, Zani ML, Quinn DJ, Dallet-Choisy S, Glasgow AMA, O'Kane C, et al. A functional variant of elafin with improved anti-inflammatory activity for pulmonary inflammation. Mol Ther. 2015;23:24–31. Dincer 38TE, Erdogan D, Gurler FG. A cutoff value for the systemic immune-inflammation index in determining activity of Behçet disease. Clin Exp Dermatol. 2021;46:286–91. Kim Y, Choi H, Jung SM, Song JJ, Park YB, Lee SW. Systemic immune-inflammation index could estimate the cross-sectional high activity and the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibodyassociated vasculitis. Nephrol (Carlton). 2019;24:711–7. Fois AG, Paliogiannis P, Scano V, et al. The systemic inflammation ındex on admission predicts ın-hospital mortality in COVID-19 patients. Molecules. 2020;25:5725. Breda L, Carbone I, Casciato I, Gentile C, Grasso EA, di Donato G, et al. Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study. Ital J Pediatr. 2021;47:237. Fu W, Ye W, Liu X, Zhu S, Fu H, Zhu R, et al. Meta-analysis of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Henoch-Schonlein purpura and its complications. Int Immunopharmacol. 2021;94:107454. Güngörer V, Dişçi I, Arslan Ş. The effect of the pretreatment systemic immuneinflammatory index and C-reactive protein-to-albumin ratio on prognosis in pediatric patients with IgA vasculitis. J Health Sci Med. 2023;6:441–8. Öksel B, Şahin N, Sönmez HE. Exploring the predictive factors in the gastrointestinal involvement of patients with immunoglobulin A vasculitis. Turk J Pediatr. 2024;66:599–607. Geng Y, Shao Y, Zhu D, Zheng X, Zhou Q, Zhou W, et al. Systemic immune-inflammation index predicts prognosis of patients with esophageal squamous cell carcinoma: A propensity score-matched analysis. Sci Rep. 2016;6:39482. Llewellyn-Jones CG, Hill SL, Stockley RA. Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro. Thorax. 1994;49:207–12. Jia WY, Zhang JJ. Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms. World J Clin Cases. 2022;10:7187–94. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Pediatric Rheumatology → Version 1 posted Editorial decision: Revision requested 21 Jul, 2025 Reviews received at journal 12 Jul, 2025 Reviewers agreed at journal 12 Jul, 2025 Reviews received at journal 29 Jun, 2025 Reviewers agreed at journal 29 Jun, 2025 Reviewers invited by journal 11 Jun, 2025 Editor assigned by journal 26 May, 2025 Submission checks completed at journal 26 May, 2025 First submitted to journal 19 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6700136","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469788350,"identity":"9a069fe7-f1a1-4e18-9deb-6bfde6942482","order_by":0,"name":"Cengiz Zeybek","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYHACNgaGAyCasYHhAwNDAmlaGGeQqIWBgZmHGC3y7T1mDz6csZMz51/c/Nm2zS6Pn72B8cPHHNxaGHvOmBvOuJFsbDnjYYNxbltysWTPAWbJmdtwa2GWyDGT5vlwIHHDjYMNybltzEBGAhszLx4tbPJvzKT/fDhQD9Jy2LKtnrAWHgkeM2mGGwcSDM43NjYzth0mrEWCJ63csOdMsuGGG4zNjD3njifO7DnYjNcv8u2Htz34ccxO3uD88ccffpRVJ/azNx/88BGPFgYGDgOofQnA8GMDsYDJAD9gfwCh+Q8AiT8EFI+CUTAKRsGIBAAHV1qu1dQ58AAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Cengiz","middleName":"","lastName":"Zeybek","suffix":""},{"id":469788351,"identity":"c8fc0c8b-8c9e-45c7-8a15-a3919305a716","order_by":1,"name":"Ahmet Bolat","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"Bolat","suffix":""},{"id":469788352,"identity":"f5de122a-c917-456d-b47e-2b593d9e4350","order_by":2,"name":"Bedriye Nuray Alpman","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Bedriye","middleName":"Nuray","lastName":"Alpman","suffix":""},{"id":469788353,"identity":"fad4b754-6508-4391-9d32-23d243a6f125","order_by":3,"name":"Tuğba İpek Karaoğlu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tuğba","middleName":"İpek","lastName":"Karaoğlu","suffix":""},{"id":469788354,"identity":"a9baf0d5-35cc-4e7f-b8cd-c5f1f36eed48","order_by":4,"name":"Nimet Öner","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Nimet","middleName":"","lastName":"Öner","suffix":""},{"id":469788355,"identity":"be818b54-86e2-48b6-8614-241263c3c713","order_by":5,"name":"Vildan Güngörer","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Vildan","middleName":"","lastName":"Güngörer","suffix":""}],"badges":[],"createdAt":"2025-05-19 14:53:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6700136/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6700136/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12969-025-01153-9","type":"published","date":"2025-09-29T15:57:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84722025,"identity":"17f8e1a6-da2b-406a-bc5b-382e02b561af","added_by":"auto","created_at":"2025-06-16 15:09:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59034,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of serum elafin levels between the active IgAV, inactive IgAV and control groups.\u003c/p\u003e\n\u003cp\u003eIgAV, IgA vasculitis\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6700136/v1/59942648a20f3363b4029186.png"},{"id":84722018,"identity":"aebd29fc-9674-411e-a2a2-8510d7c450a3","added_by":"auto","created_at":"2025-06-16 15:09:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":62142,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic (ROC) curve illustrating the sensitivity and specificity of serum elafin for diagnosis of IgA vasculitis. The dot indicates the optimal cut-off point.\u003c/p\u003e\n\u003cp\u003ePPV, positive predictive value; NPV, negative predictive value; AUC, area under curve\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6700136/v1/17e82b04557ddbeefa4523ed.png"},{"id":92884387,"identity":"80f7f988-fe89-4708-b345-e612ed3bec5b","added_by":"auto","created_at":"2025-10-06 16:12:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":925670,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6700136/v1/11fbb9a9-99b4-4ba7-8206-607142223d3d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum Elafin Levels in Patients with IgA Vasculitis: A Prospective Case-Control Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmunoglobulin A vasculitis (IgAV), formerly known as Henoch-Sch\u0026ouml;nlein purpura, is the most common type of vasculitis in children; it is characterized by the deposition of immunoglobulin A1 (IgA1)-dominant immune complexes in the walls of small vessels. Beyond its hallmark cutaneous manifestations\u0026mdash;namely, palpable purpura typically confined to the lower extremities\u0026mdash;IgAV can affect the gastrointestinal (GI) tract, joints, and kidneys [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. A critical step in the pathogenesis of IgAV involves the production of galactose-deficient IgA1 (Gd-IgA1), which, in response to a presumed infectious trigger, forms circulating immune complexes with anti-Gd-IgA1 autoantibodies; subsequently, these complexes are deposited in target tissues and activate inflammatory pathways [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eElafin and its precursor, trappin-2, along with secretory leukocyte peptidase inhibitor, are potent endogenous serine protease inhibitors and members of the chelonianin family [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Elafin exhibits a relatively narrow inhibitory profile, selectively targeting neutrophil elastase (NE), proteinase-3, pancreatic elastase and endogenous vascular elastase [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In vitro studies have demonstrated that elafin expression is upregulated in response to proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in various cell lines [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. By inhibiting NE, elafin helps mitigate excessive inflammatory responses, preventing tissue and organ damage and contributing to maintenance of a controlled and physiologically appropriate inflammatory process [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Beyond its anti-protease activity, elafin exerts anti-inflammatory effects by suppressing lipopolysaccharide (LPS) and lipoteichoic acid-stimulated nuclear factor-kappaB (NF-kappaB) activation in monocytes, resulting in reduced expression of proinflammatory cytokines [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Previous studies have reported higher levels of serum elafin in patients with Beh\u0026ccedil;et's disease, a systemic vasculitic disorder, compared to healthy controls [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeutrophils and lymphocytes are key immune system cellular components that plays critical roles in inflammation and the pathogenesis of IgAV [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. During IgAV, immune complexes contribute to disease pathogenesis by inducing NETosis via activation of FcγRIIIB or CD89 receptors [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. NETosis is a recently characterized mechanism by which neutrophils eliminate pathogens through the release of neutrophil extracellular traps (NETs) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In IgAV, elevated levels of NETs and reactive oxygen species have been observed in superficial and deep dermal perivascular tissues [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. NET levels increase significantly during the active stage of IgAV and gradually decrease during remission, with NE identified as one of the key NET-associated components [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. NE has been implicated in the regulation of elafin expression and secretion, modulating the inflammatory response [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, proinflammatory cytokines, such as IL-1β and TNF-α, play pivotal roles in the initiation and progression of vasculitis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe hypothesized that serum elafin levels may be altered in IgAV and potentially associated with disease activity and organ involvement. In addition to measuring serum elafin levels, we evaluated and compared inflammation-related parameters derived from the complete blood count (CBC), including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), between the patient and control groups. We investigated potential correlations between these parameters and serum elafin levels. To our knowledge, this is the first study to report serum elafin levels in patients with IgAV.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and Patient Selection\u003c/h2\u003e \u003cp\u003eThis single-center, prospective case\u0026ndash;control study included 51 children aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years diagnosed with IgAV and 54 age- and sex-matched healthy controls. Participants were recruited from the pediatric rheumatology outpatient clinic of our hospital between 15 April 2024 and 15 April 2025. IgAV was diagnosed based on the Ankara 2008 criteria, which have been validated by the European League Against Rheumatism, the Pediatric Rheumatology International Trials Organization, and the Pediatric Rheumatology European Society [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The control group consisted of healthy children of comparable age and sex who presented for routine follow-up examinations. These individuals had normal blood and urine test results and no history or clinical evidence of vasculitis or other chronic organ disorders, and they were not receiving any medication at the time of enrollment.\u003c/p\u003e \u003cp\u003ePatients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years who had received nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or other immunosuppressive agents for IgAV or its complications within the past 2 weeks, or had evidence of renal dysfunction (glomerular filtration rate\u0026thinsp;\u0026lt;\u0026thinsp;60 mL/min) or hepatic impairment (serum alanine/aspartate aminotransferase levels\u0026thinsp;\u0026gt;\u0026thinsp;3 x the upper reference limit) were excluded. Patients with chronic conditions, such as congenital heart disease, diabetes mellitus, autoimmune disorders, and hematological disease, a body mass index\u0026thinsp;\u0026gt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e, acute infection, or current medication use were also excluded.\u003c/p\u003e \u003cp\u003eSerum elafin levels and inflammation parameters derived from the CBC of patients with active stage IgAV (active IgAV group) were compared with those obtained during remission (inactive IgAV group) and with those of age- and sex-matched healthy controls (control group).\u003c/p\u003e \u003cp\u003e The G\u0026uuml;lhane Medical Faculty Review Board and Ethics Committee approved the study protocol. The study was performed in accordance with the Declaration of Helsinki (2024/66). Written and oral informed consent was obtained from the study paticipants.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinitions and Data Collection\u003c/h3\u003e\n\u003cp\u003eGI involvement was defined as severe abdominal pain with or without clinical indicators of GI bleeding, such as positive fecal occult blood, melena, or hematochezia. Renal involvement was defined as the presence of hematuria (\u0026gt;\u0026thinsp;5 red blood cells per high-power field in a centrifuged urine specimen) and non-nephrotic proteinuria (spot urine protein/creatinine ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.2 or 4\u0026ndash;40 mg/m\u003csup\u003e2\u003c/sup\u003e/h), or nephrotic syndrome (spot urine protein/creatinine ratio\u0026thinsp;\u0026gt;\u0026thinsp;2 or \u0026gt;\u0026thinsp;40 mg/m\u003csup\u003e2\u003c/sup\u003e/h). Scrotal involvement was defined as the presence of epididymitis, orchitis, or testicular hematoma, or testicular torsion identified on ultrasound, accompanied by scrotal and testicular pain and edema. Ultrasound confirmation was performed in all patients presenting with scrotal symptoms. GI, renal, and scrotal involvement were collectively classified as visceral involvement [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe active stage was defined as the initial phase of the disease, characterized by new-onset symptoms, whereas the inactive (remission) stage was defined by the absence of clinical signs and laboratory findings associated with disease activity [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFollowing a 12-h fast, peripheral blood samples were collected from antecubital vein of all participants to assess serum elafin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CBC parameters. In the study group, particular attention was paid to obtaining blood samples during the active stage before the initiation of NSAID and/or corticosteroid therapy, and \u0026ge;\u0026thinsp;2 weeks after discontinuation of such treatments during the inactive stage. Collected blood samples were kept at room temperature for 30 min, then centrifuged at 3,500 rpm for 10 min to obtain serum for elafin and CRP analysis. Serum samples were stored at -80\u0026deg;C until the elafin quantification. CRP and the ESR were analyzed on the same day the blood samples were collected. Serum elafin concentrations were determined using an enzyme-linked immunosorbent assay (catalogue number: E4762Hu; Bioassay Technology Laboratory, Shanghai, China), with a reported sensitivity of 0.5 ng/dL. The ESR was assessed using the Westergren method, and CRP levels were measured using an automated analyzer (AU680\u0026reg;; Beckman Coulter, Miami, FL, USA), with reference ranges of 0\u0026ndash;20 mm/h fort he ESR and 0\u0026ndash;5 mg/dL fort he CRP. CBC parameters were measured using an automated hematology analyzer (Beckman Coulter).\u003c/p\u003e \u003cp\u003eDerived CBC-based inflammatory indices included the NLR, MLR, PLR and SII. The SII was calculated using the following formula: neutrophil count (K/uL) X platelet count (K/uL) / lymphocyte count (K/uL). The NLR was calculated by dividing the neutrophil count by the lymphocyte count; the PLR by dividing the platelet count by the lymphocyte count; and the MLR by dividing the monocyte count by the lymphocyte count.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Quantitative variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range), as appropriate. Categorical variables were compared using the chi-square test. The Shapiro\u0026ndash;Wilk test was used to assess the normality of the data distribution. For comparisons between two independent groups, the independent-samples t-test was used for normally distributed variables, whereas the Mann\u0026ndash;Whitney U test was used for non-normally distributed variables. Paired (dependent) samples were analyzed using the Wilcoxon signed-rank test. Correlations between variables were evaluated using Spearman's rank correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for elafin, as well as its sensitivity and specificity for diagnosing IgAV. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBlood samples from 51 children diagnosed with IgAV during active and inactive stages were compared with those from 54 age- and sex-matched healthy controls. The mean age of the participants in the IgAV and control groups was 8.45\u0026thinsp;\u0026plusmn;\u0026thinsp;3.27 and 8.85\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84 years, respectively, with no statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.57). The IgAV group comprised 35 males (68.6%), whereas the control group included 31 males (57.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.23) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eSerum elafin levels were significantly higher in children with active IgAV (45.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11 ng/dL; range: 34.02\u0026ndash;69.28 ng/dL) compared to the control group (27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.66 ng/dL; range: 0.01\u0026ndash;41.84 ng/dL) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, leukocyte count, neutrophil count, NLR, SII, ESR, and CRP levels were significantly higher in children with active IgAV compared to healthy controls (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, 0.007, 0.006, 0.007, \u0026lt;\u0026thinsp;0.001, and \u0026lt;\u0026thinsp;0.001, respectively) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic characteristics and laboratory parameters of patients with IgAV and healthy controls\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eActive IgAV (n\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.45\u0026thinsp;\u0026plusmn;\u0026thinsp;3.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.85\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.57*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF/M (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (31.4)/35 (68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (42.6)/31 (57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.30*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocyte (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e366111.11\u0026thinsp;\u0026plusmn;\u0026thinsp;122111.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e308402.22\u0026thinsp;\u0026plusmn;\u0026thinsp;102474.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeukocyte (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9755.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3700.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7624.88\u0026thinsp;\u0026plusmn;\u0026thinsp;248.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophil (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6261.85\u0026thinsp;\u0026plusmn;\u0026thinsp;648.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4284.44\u0026thinsp;\u0026plusmn;\u0026thinsp;317.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocyte (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2683.71\u0026thinsp;\u0026plusmn;\u0026thinsp;219.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2744.88\u0026thinsp;\u0026plusmn;\u0026thinsp;114.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.29\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMonocyte (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e574.44\u0026thinsp;\u0026plusmn;\u0026thinsp;52.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e492.66\u0026thinsp;\u0026plusmn;\u0026thinsp;21.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.16\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151.34\u0026thinsp;\u0026plusmn;\u0026thinsp;70.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125.92\u0026thinsp;\u0026plusmn;\u0026thinsp;40.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.054\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e973.41\u0026thinsp;\u0026plusmn;\u0026thinsp;828.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e566.61\u0026thinsp;\u0026plusmn;\u0026thinsp;415.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElafin (ng/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESR (mm/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.33\u0026thinsp;\u0026plusmn;\u0026thinsp;10.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.51\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;12.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eData are given with mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eF,female; M,male; IgAV, IgA vasculitis; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein;\u003c/p\u003e\n\u003cp\u003e*Student t-test \u003csup\u003e\u0026dagger;\u003c/sup\u003eChi-Square test; \u003csup\u003e\u0026sect;\u003c/sup\u003eMann\u0026ndash;Whitney U test\u003c/p\u003e\n\u003cp\u003eA statistically significant difference in serum elafin levels was observed between patients with active and inactive IgAV. Elafin levels were significantly higher in the active stage (mean: 45.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11 ng/dL; median: 43.48 ng/dL; range: 34.02\u0026ndash;69.28 ng/dL) compared to the inactive stage (mean: 29.31\u0026thinsp;\u0026plusmn;\u0026thinsp;11.27 ng/dL; median: 31.84 ng/dL; range: 11.54\u0026ndash;43.18 ng/dL) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, the ESR, CRP levels, NLR, and SII levels were significantly higher in patients with active IgAV compared to those with inactive IgAV (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008, \u0026lt;\u0026thinsp;0.001, 0.006, and 0.035, respectively), with the highest levels observed in active IgAV group and the lowest in the healthy controls. However, no statistically significant differences were observed between the inactive IgAV group and healthy controls in these parameters (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In addition, no significant differences were observed in the PLR or MLR among the active IgAV, inactive IgAV, and control groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLaboratory measurements in active IgAV, inactive IgAV and control groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eActive IgAV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInactive IgAV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep (active-control)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep (inactive-control)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep (active-inacvtive)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElafin (ng/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11\u003c/p\u003e\n \u003cp\u003e43.48 (13.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.31\u0026thinsp;\u0026plusmn;\u0026thinsp;11.27\u003c/p\u003e\n \u003cp\u003e31.84 (6.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.66\u003c/p\u003e\n \u003cp\u003e31.50 (5.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.65\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESR (mm/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.33\u0026thinsp;\u0026plusmn;\u0026thinsp;10.97\u003c/p\u003e\n \u003cp\u003e12 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.19\u003c/p\u003e\n \u003cp\u003e5 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.51\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e\n \u003cp\u003e5 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.6\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;12.03\u003c/p\u003e\n \u003cp\u003e5.2 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.49\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003c/p\u003e\n \u003cp\u003e1.6 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e\n \u003cp\u003e1.1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.098\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\n \u003cp\u003e1.97 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e\n \u003cp\u003e1.67 (0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n \u003cp\u003e1.4 (0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.065\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151.34\u0026thinsp;\u0026plusmn;\u0026thinsp;70.17\u003c/p\u003e\n \u003cp\u003e123.68 (83.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e127.47\u0026thinsp;\u0026plusmn;\u0026thinsp;35.54\u003c/p\u003e\n \u003cp\u003e120.36 (55.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125.92\u0026thinsp;\u0026plusmn;\u0026thinsp;40.06\u003c/p\u003e\n \u003cp\u003e117.08 (56.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.054\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.73\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\n \u003cp\u003e0.21 (0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\n \u003cp\u003e0.18 (0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\n \u003cp\u003e0.17 (0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.81\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.89\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e973.41\u0026thinsp;\u0026plusmn;\u0026thinsp;828.85\u003c/p\u003e\n \u003cp\u003e638.22(437.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e635.43\u0026thinsp;\u0026plusmn;\u0026thinsp;377.33\u003c/p\u003e\n \u003cp\u003e494.81 (373)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e566.61\u0026thinsp;\u0026plusmn;\u0026thinsp;415.85\u003c/p\u003e\n \u003cp\u003e477.71(284.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.42\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are given with mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median (interquartile range)\u003c/p\u003e\n\u003cp\u003eIgAV, IgA vasculitis; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eMann\u0026ndash;Whitney U test; *Wilcoxon test\u003c/p\u003e\n\u003cp\u003eSerum elafin levels, as presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, were subjected to pairwise comparisons among the study groups, and the results were visualized using a box plot (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the association between serum elafin levels and specific organ involvement in IgAV patients. No statistically significant differences in serum elafin levels were observed between patients with and without skin or joint involvement (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.56 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.061, respectively). In contrast, patients with GI, renal, or scrotal involvement exhibited significantly higher serum elafin levels compared to those without these manifestations (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022, respectively) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical manifestations in patients with active IgAV and their association with serum elafin levels\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePresence\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eElafin (ng/dL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOnly skin involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes n:20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo n:31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.77\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e\n \u003cp\u003e43.48 (9.26)\u003c/p\u003e\n \u003cp\u003e47.26\u0026thinsp;\u0026plusmn;\u0026thinsp;12.91\u003c/p\u003e\n \u003cp\u003e42.89 (25.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJoint involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes n:13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo n:38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.25\u003c/p\u003e\n \u003cp\u003e37.02 (32.44)\u003c/p\u003e\n \u003cp\u003e49.21\u0026thinsp;\u0026plusmn;\u0026thinsp;11.66\u003c/p\u003e\n \u003cp\u003e46.19 (35.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.061\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGIS involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes n:15\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo n:36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.91\u0026thinsp;\u0026plusmn;\u0026thinsp;14.63\u003c/p\u003e\n \u003cp\u003e62.65 (24.96)\u003c/p\u003e\n \u003cp\u003e43.43\u0026thinsp;\u0026plusmn;\u0026thinsp;9.41\u003c/p\u003e\n \u003cp\u003e40.17 (10.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKidney involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes n:6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo n:45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.16\u0026thinsp;\u0026plusmn;\u0026thinsp;9.81\u003c/p\u003e\n \u003cp\u003e59.25 (13.88)\u003c/p\u003e\n \u003cp\u003e41.33\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62\u003c/p\u003e\n \u003cp\u003e40.05 (11.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScrotal involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes n:3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo n:48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.83\u0026thinsp;\u0026plusmn;\u0026thinsp;9.34\u003c/p\u003e\n \u003cp\u003e64.87\u003c/p\u003e\n \u003cp\u003e44.51\u0026thinsp;\u0026plusmn;\u0026thinsp;10.23\u003c/p\u003e\n \u003cp\u003e41.76 (12.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.022\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e\u0026sect;\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are given with mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median (interquartile range)\u003c/p\u003e\n\u003cp\u003eGIS, gastrointestinal system\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eMann\u0026ndash;Whitney U test\u003c/p\u003e\n\u003cp\u003eNo statistically significant correlations were observed between serum elafin levels and the PLR or MLR (r\u0026thinsp;=\u0026thinsp;0.036, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.76; and r\u0026thinsp;=\u0026thinsp;0.045, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.741, respectively). Conversely, serum elafin levels demonstrated a moderate positive correlation with ESR (r\u0026thinsp;=\u0026thinsp;0.418, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and CRP (r\u0026thinsp;=\u0026thinsp;0.547, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, weak positive correlations were observed between serum elafin levels and the NLR (r\u0026thinsp;=\u0026thinsp;0.355, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) and the SII (r\u0026thinsp;=\u0026thinsp;0.347, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation between serum elafin levels and inflammatory parameters\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eElafin\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.547\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.741\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eESR, erythrocyte sedimentation rate; CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; SII, systemic immune-inflammation index.\u003c/p\u003e\n\u003cp\u003er: Spearman\u0026rsquo;s correlation coefficient.\u003c/p\u003e\n\u003cp\u003eROC curve analysis for the diagnosis of IgAV identified an optimal serum cut-off value of 35.38 ng/dL. At this threshold, serum elafin exhibited a sensitivity of 86.2% and a specificity of 77.8%, with a positive predictive value (PPV) of 17.34% and a negative predictive value (NPV) of 89.64% (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCut off:\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e35.88 ng/dL\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.34%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89.64%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.924\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPV, positive predictive value; NPV, negative predictive value; AUC, area under curve\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe evaluated serum elafin levels in patients with IgAV during active and inactive disease stages, comparing these levels with those of healthy controls. Our findings revealed that serum elafin levels were significantly higher during the active stage of IgAV compared to the inactive stage and healthy controls, indicating a potential role of elafin as a biomarker for disease activity.\u003c/p\u003e \u003cp\u003eElafin modulates inflammation and innate imm\u0026uuml;ne responses by inhibiting key transcription factors, such as activator protein-1 and NF-kappaB. This regulatory effect is mediated through suppression of the ubiquitin-proteasome pathway and upregulation of the NF-kappaB inhibitor, IkappaBalpha [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, the precise mechanisms underlying this inhibitory pathways remain uncertain [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In mouse models of LPS-induced inflammation, elafin has accelerated resolution by enhancing neutrophil apoptosis via NF-kappaB modulation; this pro-resolving effect may be attributed to the inhibition of NE and possibly the preservation of intact annexin-1 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Furthermore, elafin may prevent NE-mediated cleavage of dendritic cell receptors, such as CD40, CD80 and CD86, facilitating apoptotic cell clearance and the resolution of inflammation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In mouse models of colitis, elafin-expressing mice demonstrated reduced inflammatory cell infiltration, attenuated tissue damage, and suppression of pro-inflammatory cytokines, such as IL-16 and 17, and chemokines [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, the anti-inflammatory effects of elafin may involve increased secretion of IL-10 and decreased secretion of IL-8 via NF-kappaB inhibition [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn normal skin samples, no elafin immunoreactivity was observed in the vascular walls. In contrast, elafin immunoreactivity was demonstrated in the endothelial cells of small vessels in the superficial dermis and in intravascular fibrin deposits; these findings suggest a potential role for elafin in fibrin stabilization during vascular injury [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Similar patterns of elafin expression have been reported in other vasculitides, including microscopic polyangiitis and giant cell arteritis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Notably, elafin immunoreactivity was not observed in Churg-Strauss syndrome, a condition characterized by predominant eosinophilic rather than neutrophilic infiltration, reinforcing the association between neutrophil activity and elafin expression [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Neutrophil infiltration and the release of NE at sites of vascular injury may initiate a self-perpetuating cycle of tissue damage. NE degrades elastin, and the resulting elastin-derived peptides can attract additional neutrophils, exacerbating inflammation and injury [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Elafin interrupts this destructive feedback loop by inhibiting NE activity and reducing elastin-induced neutrophil chemotaxis [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eElafin is upregulated at sites of inflammation and may play a role in modulating the inflammatory response [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. For instance, elevated serum elafin levels have been positively correlated with disease activity in inflammatory bowel disorder, and elafin has been proposed as a potential biomarker in ulcerative colitis [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In Beh\u0026ccedil;et's disease, another vasculitis, serum elafin levels were significantly higher during the active disease stage compared to healthy controls, with particularly significant elevations in patients presenting with arthritis, suggesting its potential utility as a disease activity marker in this subgroup [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Consistent with these findings, our findings support the notion that elafin may serve as a biomarker reflecting disease activity in IgAV.\u003c/p\u003e \u003cp\u003eDespite its high sensitivity, elafin exhibited a low PPV (17.34%) in our study, indicating that elevated serum elafin levels may be observed in a variety of inflammatory conditions beyond IgAV. Conversely, the NPV (89.64%) indicates that low serum elafin levels may be useful in excluding active IgAV, supporting its potential role as a negative biomarker in clinical practice.\u003c/p\u003e \u003cp\u003eThe administration of elafine via intravenous, intranasal, or aerosolized routes has been demonstrated to be safe and potentially protective in various cardiovascular or pulmonary disorders [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. For instance, in murine models, recombinant human elafin mitigates bronchopulmonary dysplasia by inhibition apoptosis and suppressing the release of inflammatory cytokines, primarily via the modulation of NF-kappaB activity [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Phase 1 and 2 clinical trails of intravenous elafin have confirmed its safety profile, with no reported drug-related adverse effects [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Our findings suggest a potential role for elafin in the pathogenesis of vasculitis and raise the possibility that supraphysiologic doses or variants of elafin may hold therapeutic potential in the future [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCBC-derived parameters are considered rapid, simple, and cost-effective indicators of systemic inflammation and immune response. Among these, the SII, NLR, MLR, and PLR are commonly used indices derived from standart CBC results. Considering their capacity to reflect inflammatory status, these ratios are increasingly used as surrogate markers of inflammatory burden in various disease states. For instance, the SII has been demonstrated to be a reliable marker for assessing disease severity in anti-neutrophil cytoplasmic antibody-associated vasculitis and Beh\u0026ccedil;et's disease, as well as for predicting mortality in COVID-19 [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. We observed elevated ESR, CRP levels, and NLR in patients with active IgAV, consistent with prior studies [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Furthermore, serum elafin levels were positively correlated with the ESR, CRP, NLR, and SII, reinforcing its potential as an inflammatory marker. Although limited studies have evaluated the SII in IgAV, G\u0026uuml;ng\u0026ouml;rer et al. [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] reported that SII is a valuable parameter for detecting visceral involvement, and \u0026Ouml;ksel et al. [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] identified the SII as a predictor of GI complications. Although these previous studies focused on internal comparisons within IgAV cohorts, our study demonstrated a significantly higher SII in patients with active IgAV compared to healthy controls. Consistent with prior study, we observed elevated SII value in IgAV patients with visceral involvement [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Among systemic inflammatory markers, the SII is considered a more objective and comprehensive indicator of the balance between pro-inflammatory and immune responses than the PLR, NLR, or MLR [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has several strengths. First, to our knowledge, this is the first study to evaluate serum elafin levels in pediatric patients with IgAV. Second, the intra-individual comparison between active and inactive disease stages allows for a more precise assessment of disease-related changes, minimizing inter-individual variability. Third, blood samples were collected before the administration of immunosuppressive therapies, eliminating potential confounding effects of medications, particularly corticosteroids [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, our study has several limitations. The relatively small sample size may limit the generalizability of the findings. Moreover, patients with less common organ involvement, such as the central nervous system or the urogenital tract involvement such as the ureter, were not represented in the cohort, precluding analysis of elafin expression in these manifestations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings suggest that serum elafin levels are significantly elevated in children with active IgAV compared to those in remission and healthy controls. Elafin may serve as a valuable biomarker for disease activity and visceral involvement in IgAV. Moreover elafin could play a mechanistic role in disease pathogenesis by modulating inflammation and vascular injury. Further larger multicenter studies are needed to elucidate the role of elafin across diverse clinical phenotypes of IgAV and to evaluate the therapeutic potential of elafin and its variants in vasculitic disorders.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIgAV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Immunoglobulin A Vasculitis\u003c/p\u003e\n\u003cp\u003eIgA1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Immunoglobulin A1\u003c/p\u003e\n\u003cp\u003eCRP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; C-reactive protein\u003c/p\u003e\n\u003cp\u003eESR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Erythrocyte Sedimentation Rate\u003c/p\u003e\n\u003cp\u003eGI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Gastrointestinal\u003c/p\u003e\n\u003cp\u003eGd-IgA1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Galaktose-deficient IgA1\u003c/p\u003e\n\u003cp\u003eNE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil elastase\u003c/p\u003e\n\u003cp\u003eIL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Interleukine\u003c/p\u003e\n\u003cp\u003eTNF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Tumour Necrosis Factor\u003c/p\u003e\n\u003cp\u003eLPS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Lipopolysaccharide\u003c/p\u003e\n\u003cp\u003eNF-kappaB \u0026nbsp; \u0026nbsp; Nuclear factor-kappaB\u003c/p\u003e\n\u003cp\u003eCD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cluster of differentiation\u003c/p\u003e\n\u003cp\u003eNETs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil ekstraselular traps\u003c/p\u003e\n\u003cp\u003eNLR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil-to-lymphocyte ratio\u003c/p\u003e\n\u003cp\u003eMLR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Monocyte-to-lymphocyte ratio\u003c/p\u003e\n\u003cp\u003eSII \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Systemic immune-inflammation\u003c/p\u003e\n\u003cp\u003eCBC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Complete Blood Count\u003c/p\u003e\n\u003cp\u003eNSAID \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Nonsteroidal anti-inflammatory drug\u003c/p\u003e\n\u003cp\u003eSD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Standart deviation\u003c/p\u003e\n\u003cp\u003eROC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n\u003cp\u003eM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n\u003cp\u003eGIS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Gastrointestinal system\u003c/p\u003e\n\u003cp\u003ePPV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Positive predictive value\u003c/p\u003e\n\u003cp\u003eNPV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Negative predictive value\u003c/p\u003e\n\u003cp\u003eAUC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Area under curve\u003c/p\u003e\n\u003cp\u003eCOVID \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Coronavirus disease\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI am extremely thankful to Dr. Çiğdem YÜCEL for help in ELISA studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCame up with the study’s concept and design: C.Z., A.B., VG; The data collection was carried out: C.Z., B.N.A., N.Ö., V.G.; Were responsible for analyzing and interpreting the results: C.Z., A.B., V.G.; The initial draft of the paper was prepared: C.Z., A.B., V.G.; The ethics committee approval process: C.Z., T.İ.K.;,The results were evaluated by all authors, who then approved the final version of this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs far as funding is concerned, the authors did not get any financial assistance for research and/or authorship of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset used/analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Gülhane Medical Faculty Review Board and Ethics Committee and conducted to the principles of the Helsinki Declaration (2024/66). \u0026nbsp;Written and oral informed consent was collected for all subjects. \u0026nbsp; The study was approved by the Institutional Ethics Committee prior to study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYal\u0026ccedil;ındag A, Sundel R. 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Systemic immune-inflammation index predicts prognosis of patients with esophageal squamous cell carcinoma: A propensity score-matched analysis. Sci Rep. 2016;6:39482.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLlewellyn-Jones CG, Hill SL, Stockley RA. Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro. Thorax. 1994;49:207\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJia WY, Zhang JJ. Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms. World J Clin Cases. 2022;10:7187\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Children, IgA vasculitis, Elafin, Biomarker, Inflammation","lastPublishedDoi":"10.21203/rs.3.rs-6700136/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6700136/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eImmunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis characterized by perivascular IgA deposition and neutrophil activation. Elafin, an anti-inflammatory and anti-protease protein expressed by epithelial and select immune cells, may play a role in modulating vascular inflammation. We evaluated serum elafin levels in pediatric patients with IgAV during active stage and remission, and investigated their associations with disease activity, organ involvement, and systemic inflammatory markers.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-center prospective case-control study included 51 pediatric patients diagnosed with IgAV and 54 age- and sex-matched healthy controls. Paired data were obtained from the same IgAV patients during the remission phase, allowing intra-individual comparisons. Serum elafin levels were quantified using enzyme-linked immunosorbent assay (ELISA). Inflammatory parameters, including complete blood counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were assessed in all participants.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSerum elafin levels were significantly elevated in patients with IgAV (45.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11 ng/dL; range: 34.02\u0026ndash;69.28) compared to healthy controls (27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.66 ng/dL; range: 0.01\u0026ndash;41.84) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with the highest concentrations observed during active disease stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients with visceral involvement (gastrointestinal, renal, or scrotal) exhibited significantly higher elafin levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas no significant association was found with isolated skin or joint involvement. Serum elafin levels demonstrated positive correlations with the ESR (p\u0026thinsp;=\u0026thinsp;0.001, r\u0026thinsp;=\u0026thinsp;0.418), CRP (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, r\u0026thinsp;=\u0026thinsp;0.547), neutrophil-to-lymphocyte ratio (p\u0026thinsp;=\u0026thinsp;0.002, r\u0026thinsp;=\u0026thinsp;0.355), and systemic immune-inflammation index (p\u0026thinsp;=\u0026thinsp;0.003, r\u0026thinsp;=\u0026thinsp;0.347). Receiver operating characteristic curve analysis identified an optimal serum elafin cut-off value of 35.38 ng/dL for distinguishing active IgAV, yielding a sensitivity of 86.2% and specificity of 77.8%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSerum elafin levels were significantly elevated during the active stage of IgAV and may serve as a potential biomarker for disease activity, particularly in patients with visceral involvement.\u003c/p\u003e","manuscriptTitle":"Serum Elafin Levels in Patients with IgA Vasculitis: A Prospective Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-16 15:08:20","doi":"10.21203/rs.3.rs-6700136/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-21T10:18:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-12T15:57:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4399820407756749911449162476632634493","date":"2025-07-12T12:57:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-29T16:37:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244660000320602017511518997215082362297","date":"2025-06-29T10:06:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-11T11:40:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-26T15:41:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-26T15:39:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Rheumatology","date":"2025-05-19T14:50:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d31a236d-b765-40d4-883f-4737cd25a3f2","owner":[],"postedDate":"June 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:08:30+00:00","versionOfRecord":{"articleIdentity":"rs-6700136","link":"https://doi.org/10.1186/s12969-025-01153-9","journal":{"identity":"pediatric-rheumatology","isVorOnly":false,"title":"Pediatric Rheumatology"},"publishedOn":"2025-09-29 15:57:25","publishedOnDateReadable":"September 29th, 2025"},"versionCreatedAt":"2025-06-16 15:08:20","video":"","vorDoi":"10.1186/s12969-025-01153-9","vorDoiUrl":"https://doi.org/10.1186/s12969-025-01153-9","workflowStages":[]},"version":"v1","identity":"rs-6700136","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6700136","identity":"rs-6700136","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}