Observation on The Formation of Neutrophil Extracellular Traps in Psoriatic Peripheral Blood

Observation on The Formation of Neutrophil Extracellular Traps in Psoriatic Peripheral Blood | 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 Observation on The Formation of Neutrophil Extracellular Traps in Psoriatic Peripheral Blood Pan Chen, Xiao-yan Qu, Wen-qiong Ni, Hui Xiao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8577940/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objective To explore the clinical application value of Neutrophil extracellular traps (NETs) in evaluating psoriasis. Methods 2ml peripheral blood of 63 patients with psoriasis and 27 healthy controls were collected. Neutrophils were isolated by density gradient method, and the formation of NETs was observed by immunofluorescence staining. We then calculated the proportion and fluorescence intensity of NETs and analyzed their correlation with clinical classification, severity, and serological indicators. Furthermore, the skin lesions of 5 patients with psoriasis were collected, and the NETs were observed by immunofluorescence method. Results The proportion and fluorescence intensity of spontaneous NETs in patients with psoriasis were significantly higher than those in healthy controls and were positively correlated with the PASI scores. The generation of NETs in psoriasis patients with metabolic syndrome (MetS) or high-TNF-α was higher than in psoriasis patients without metabolic abnormalities or normal-TNF-α. NETs were also observed in most psoriatic skin specimens. Conclusions The levels of NETs are correlated with the disease severity of psoriasis and patients with metabolic abnormalities and may be used as a clinical indicator to reflect the inflammatory state of psoriasis and metabolic comorbidity of psoriasis for disease evaluation. Psoriasis metabolic syndrome Neutrophil Extracellular Traps Figures Figure 1 Figure 2 Figure 3 Introduction Psoriasis is a common, chronic inflammatory skin disease with a high incidence that can occur in adults and children [12] . Generalized skin lesions throughout the body bring substantial economic and psychological burdens to individuals [2] . In addition to psoriasis, patients are more likely to have certain other systemic diseases, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, and autoimmune diseases, generally considered to be comorbidities of psoriasis [14] . However, the mechanism of psoriasis and its comorbidity is still unclear.Existing studies believe it is caused by genetic and environmental factors [13] . In addition, a variety of traditional immune cells like T cells, dendritic cells, and neutrophils, as well as non-traditional immune cells like keratinocytes, contribute to the development of psoriasis. Neutrophils, despite their brief lifespan, may also have a role in this process [6] . Neutrophils are attracted to areas of psoriasis, especially in the epidermis, where they come together to create Kogoj spongiform pustules in the stratum spinosum and Munro microabscesses in the stratum corneum [30] . The exact contribution of neutrophils to the development of psoriasis remains unclear, but evidence from cases of drug-induced agranulocytosis leading to improvement and subsequent relapses upon neutrophil count normalization indicates a significant involvement of neutrophils [6] . Additionally, neutrophils can take the lead in capturing exogenous stimuli such as bacteria and viruses and release neutrophil extracellular traps (NETs) through a unique death mechanism [9] . Brinkmann et al. described this mechanism in 2004: Histone 3(H3) citrullination modification uncoilates chromatin, eventually leading to the programmed externalization of grain-derived protein-modified chromatin fiber networks (NETs). This process is named NETosis [4] . In the process of NETosis, NETs serve as a natural biological defense mechanism, and their elevation is associated with inflammatory response and related diseases such as obesity, atherosclerosis, and cancer [3,8] . Moreover, it acts as an autoantigen associated with various autoimmune diseases [25] . The exact contribution of NETosis to the development of psoriasis remains uncertain at this time. This research examined the creation of NETs by neutrophils in the peripheral blood and skin sores of individuals with psoriasis, with or without metabolic syndrome, in comparison to individuals without any health issues.In addition, we examined the relationship between NETs and clinical categorization, severity of illness, and markers of inflammation in order to offer insight into the role of neutrophils in the development of psoriasis.Thus, these findings illustrate a novel mechanism by which NETs promote a sustained inflammatory response in pso Methods 2.1.1 Recruitment of patients. The Department of Dermatology at Zhengzhou University's central hospital enrolled 63 individuals diagnosed with psoriasis.Furthermore, 27 individuals without health issues were enlisted through advertising.Blood samples were collected from both patients and healthy individuals through peripheral veins.At the time of blood sampling, information was gathered on the type of psoriasis, the existence of psoriatic arthritis, the severity of the disease, and the treatments used for psoriasis (such as topical therapy, phototherapy, immunosuppressive drugs, and biological agents).The severity of psoriasis in each patient was assessed by the PASI score and BSA, which measures the seriousness of skin lesions and the extent of the affected area.Approval for the study was granted by the ethics committee at Zhengzhou University Affiliated Zhengzhou Central Hospital, and the research was carried out in compliance with the Declaration of Helsinki.All patients and healthy controls provided written informed consent before participating in the study. 2.1.2 Isolation of peripheral blood neutrophils. Neutrophils from peripheral blood were separated using centrifugation with a density gradient.Histopaque-1119 (11191) and Histopaque-1077 (10771) were bought from Sigma-Aldrich, while red blood cell lysate (R1010) was bought from Beijing Solaibao Technology Co., LTD. A mixture of Histopaque-1119 4mL, Histopaque-1077 2mL, and fresh peripheral blood 2mL (collected within 1 hour) was gently added to a 15 ml centrifuge tube, then centrifuged at 700g for 30 minutes at room temperature.Plasma layer from top to bottom, respectively, a single nuclear cell layer, layer, neutrophils, Histopaque Histopaque - 1077-1119, the red blood cells layer.With aseptic suction drain neutrophils layer cell suspension, PBS washing, again after red blood cell cracking liquid soluble red treatment for immunofluorescence staining. 2.1.3 Visual quantification of NETosis by fluorescence microscopy. The formation of NETs was observed by immunofluorescence staining.Neutrophils from human peripheral blood were cultured in complete medium (CM - H197) obtained from Wuhan Puno Life Technology Co., Ltd. The cells were supplemented with closed goat serum (SL038) from Mr. Lai Treasure Technology Co., Ltd. Additionally, a rabbit anti-histone H3 (citrulline R2 + R8 + R17) polyclonal antibody (ab5103), a murine anti-MPO monoclonal antibody (ab25989), ALexarFluor 488-labeled goat anti-rabbit IgG secondary antibody (ab150077), and ALexarFluor 594 labeled goat anti-mouse IgG secondary antibody (ab150116) were all purchased from Abcam.Fluorescence quenching sealing tablet (DAPI) resistance (P0131) purchased from Beijing blue skies biotechnology co., LTD.Isolate fresh neutrophils from peripheral blood, suspend in complete medium, adjust cell density to 100 x 104 / mL, seed cells onto 6-well plates coated with poly lysine, add 200 ul of cell suspension to each well, incubate for 1 hour, fix with 4% formaldehyde for 20 minutes, permeabilize with 0.2% Triton X-100 for 10 minutes, block with goat serum for 1 hour, incubate with antibodies against H3Cit and MPO overnight at 4 ℃, wash with PBS, incubate with fluorescent secondary antibodies at room temperature for 1 hour in the dark.After washing three times with PBS again, the slides were sealed with anti-fluorescence quenching mounting solution containing DAPI, and then observed under a fluorescence microscope.Images were taken using Image View software, and fluorescence image analysis was performed using ImageJ software. 2.1.6 Immunofluorescence staining. After fixing the cells with a 4% formaldehyde solution, they were then washed with PBS.Subsequently, the cells were treated with a 0.5% solution of octylphenol polyethylene glycol ether for 20 minutes at ambient temperature, followed by a PBS rinse.The cells were blocked with 5%BSA solution for 30min at room temperature.The initial antibody was prepped and then applied to every slide in the sealed well plate, followed by an overnight incubation at 4℃.After that, the slides were submerged in a PBST solution and left to interact with the secondary antibody for 1 hour at room temperature in darkness.DAPI staining solution was added for 5min.Finally, it was observed under the microscope. 2.1.7 Statistical analysis. GraphPad Prism 7 software was utilized for all statistical analyses, with error bars representing standard error of the mean (s.e.m).or s.d.The figure legends provide details on the number of trials, occurrences, and statistical methods used in each independent experiment. Results 3.1.1 Clinical features of patients. Characteristics of individuals in a clinical setting.63 patients with psoriasis were examined in this research, where we studied neutrophils in peripheral blood and sera.The average age of individuals with psoriasis was 40.68 years, with a standard deviation of 12.44.There were 42 males and 21 females (Table 1) . The clinical subtype was psoriasis vulgaris in 39 cases, guttate psoriasis in 11 cases, erythrodermic psoriasis in 5 cases， pustular psoriasis in 6 cases, and articular psoriasis in 2 cases.In 4 instances, the Psoriasis Area and Severity Index (PASI) rating was less than 10, while it fell between 10 and 20 in 22 cases, 20 and 30 in 29 cases, and 30 and 40 in 8 cases.Treatment options for psoriasis patients at the time of blood sampling included no treatment (11 patients), topical therapy (42 patients with topical steroids, vitamin D analogs, and retinoids), ultraviolet light phototherapy (32 patients), methotrexate (12 patients), cyclosporine (9 patients), and secukinumab (5 patients).Additionally, we incorporated 27 individuals without health issues in our research, with an average age of 39.33 years and a standard deviation of 11.86 years, consisting of 15 men and 12 women.Notably, there was no statistically significant difference in age between psoriasis patients and healthy controls ( P =0.638). 3.1.2 Formation of NETs in skin lesions of psoriasis NETs formation was detected in psoriasis skin lesions using a fluorescence microscope.The results showed that positive expression of H3Cit was observed in Munro micro-abscess of skin lesions from psoriasis patients (Figure 1) . 3.1.3 A comparison of spontaneous NETs in peripheral blood between the psoriasis and healthy control groups. The morphology and number of NETs were observed under a fluorescence microscope, and the visual fields were randomly selected under 200 × magnification for each sample.ImageJ software was used to analyze the fluorescence intensity and semi-quantitative count.The number of H3Cit (+) cells/DNA (+) cells in each field of view was used as the positive rate of NETs, and the green fluorescence of H3Cit represented the fluorescence intensity and area of NETs.The findings indicated a higher positivity rate of NETs, total fluorescence intensity, average fluorescence intensity, and fluorescence area of H3Cit in the peripheral blood of psoriasis patients compared to the healthy control group.Similarly, there was a statistically significant variation ( P < 0.01) (Figure 2, Table 2). 3.1.4 The severity of psoriasis is directly related to the positivity rate of NETs. To understand the possibility of NETs as a clinical indication of psoriasis, we evaluated the correlation between the development of NETs and the severity of psoriasis.A Pearson's test was used to analyze the correlation between the positive rate of NETs and PASI and BSA scores.The findings were as follows: The presence of NETs in peripheral blood was directly associated with the severity of psoriasis as measured by the PASI score (r=0.31, P =0.013). However, these were not significantly correlated with the BSA score (r=0.17, P =0.175) ( Figure 3 ). 3.1.5 Comparative analysis of spontaneous NETs among different types of psoriasis. To understand the relationship between the formation of NETs and the classification of psoriasis, we compared the formation of NETs in different types of psoriasis.The findings indicated that there were no notable variances in the positivity rate, overall brightness level, fluorescence distribution, and mean brightness level of NETs across the various psoriasis categories (Kruskal-Wallis Test was used for multiple group comparison, Mann-Whitney U test was used for comparison between the two groups, P > 0.05; Table 3 ). 3.1.6 Correlation analysis between peripheral blood NETs and laboratory results of psoriasis. Retrospectively, we gathered clinical data including blood glucose, blood lipid, blood uric acid, Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), C-reaction protein (CRP), and Procalcitonin (PCT).The psoriasis group was divided into a normal result group and an abnormal result group.PASI, BSA, and spontaneous NETs between the two groups were analyzed.The fluorescence area of NETs in the group with metabolic abnormalities was notably greater compared to the group without metabolic abnormalities, with statistical significance ( P < 0.05). Moreover, the combined fluorescence intensity and area of NETs in the high TNF-α category were notably greater compared to the normal TNF-α group ( P < 0.05).No notable variations were observed in the positivity rate of NETs, the ratio of fluorescence, overall fluorescence strength, mean fluorescence strength, PASI, and BSA ratings between the elevated IL-6, CRP, and PCT categories, and the standard IL-6, CRP, and PCT categories ( P > 0.05) ( Table 4 ). Discussion Genetic and environmental factors are closely related to the pathogenesis of psoriasis [19] . In the interplay between genetic susceptibility and environmental triggers, infection related to microbiota invasion may be a key player [26] . Neutrophils, as immune cells in the early response to infection, play a role after receiving stimulation from microorganisms related to the inflammatory immune response in psoriasis [5] . Neutrophils are crucial in the development of psoriasis.As a "pioneer soldier" in the innate immune response, it can transform into NETs through phagocytosis, degranulation, or activation to participate in the immune response [18] . Studies have shown that the depletion of neutrophils can alleviate psoriasis-like skin lesions in psoriasis-like mouse models [28] . Notably, psoriatic lesions improve in patients with drug-induced agranulocytosis, while psoriasis recurs after normalization of neutrophil counts [31] . Moreover, some studies have found that the content of NETs in skin lesions of patients with psoriasis is significantly increased [24] . In a mouse model of psoriasis induced by imiquimod, the continuous intravenous administration of CI-amide for a week (which decreased the production of NETs) led to a significant decrease in the levels of NETs in the bloodstream, the infiltration of T cells and neutrophils in the dermis, and the release of inflammatory mediators in skin cells.Reducing the release of NETs can greatly alleviate psoriasis by significantly decreasing the hypertrophy of the scale and spinous layer of the back skin in mice [29] . The research discovered a rise in NETs formation in the bloodstream of psoriasis patients, which was linked to higher PASI scores, indicating a potential role of neutrophils in the development of psoriasis through NETs formation.However, the specific mechanism is still unclear.Existing studies have found that NETs can promote a large number of non-activated neutrophils to chemotaxis, migration to the epidermis, and further secretion of NETs, forming a self-amplifying immune activation cycle based on repeated activation of neutrophils [15] . In this cycle, the continuously released NETs activate PDCS, stimulate keratinocytes, and interact with Th17 to release many chemokines and inflammatory mediators, ultimately leading to psoriasis occurrence and development.Therefore, detecting NETosis cells in peripheral blood may be used as an inflammatory indicator to evaluate the condition of patients with psoriasis or provide a basis for treating targeted neutrophils. The current research also identified a connection between serum TNF-α levels and NETs in individuals diagnosed with psoriasis.This correlation has also been reported in rheumatoid arthritis31 and radiation-induced axial spondylarthritis [27] . The latter found reduced NETosis production after infliximab (a TNF-α inhibitor) treatment.Other studies have found that in patients with rheumatoid arthritis, infliximab treatment can inhibit the formation of NETs, reduce the production of inflammatory mediators, and improve disease activity [7] . These results suggest that TNF-α may promote the formation of NETs, and NETs may be one of the indicators for evaluating the efficacy of TNF-α monoclonal antibody in treating psoriasis. Recent research has shown a strong connection between the production of NETs and the development of different non-infectious acute and chronic illnesses in recent years [16] . Environmental factors such as microbial infection, stress, smoking, obesity, and alcohol consumption, as the critical risk factors and triggers of psoriasis, have systemic effects on the body [1] . Therefore, psoriasis is often co-morbid with other diseases and added clinical studies have confirmed that psoriasis is often combined with metabolism-related diseases [21] . Metabolic syndrome has been proposed to elevate the likelihood of cardiovascular disease and early mortality in individuals with psoriasis, leading to a notable decrease in their lifespan [11] . Long-term metabolic disorders in these comorbidities can cause long-term activation of innate immunity, resulting in long-lasting metabolic inflammation [20] . Likewise, the oxidative stress environment and inflammatory factors produced by inflammatory cells provide a favorable microenvironment for the process of NETosis, causing psoriasis recurrence under the influence of a trigger factor [17] . Furthermore, research has indicated a notable rise in the creation of NETs in individuals with type 2 diabetes mellitus and the related atherosclerosis. ApoE -/- mice that suppress NETosis by eliminating NE and protease-3 exhibit significantly decreased AS lesions in comparison to ApoE -/- knockout mice [22] . Subjects with metabolic syndrome and type 1 diabetes were treated with Secukinumab (an effective biological agent for treating plaque psoriasis).The average body weight, waist circumference, and BMI of those who responded positively decreased in comparison to the control group [10] . These findings suggest that NETs are closely associated with psoriasis and its metabolism-related comorbidities.This study showed that patients with psoriasis and metabolic abnormalities had increased spontaneous NETs compared to those without.Furthermore, NETs may be one of the mechanisms linking psoriasis and its comorbidities.Notably, drugs targeting neutrophils, especially NETs, may become one of the therapeutic targets for psoriasis.Dimethyl fumarate, a therapeutic drug for psoriasis, can weaken the function of neutrophils and inhibit the formation of NETs, which corroborates the possibility of NETs as a therapeutic target for psoriasis [23] . Acute infection is a key factor in psoriasis's trigger and relapse mechanism, and neutrophils are the "seeds" of the early response to acute infection.The inflammatory state in patients with metabolic disorders provides "fertile soil" for this process, promoting neutrophil NETosis to release NETs.Furthermore, the inflammatory immune reaction quickly spreads and intensifies, ultimately resulting in the onset, progression, and reappearance of psoriasis.However, the specific mechanism of this process still needs further exploration and research. Declarations Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Contribution The corresponding author is responsible for data curation, supervision and writing - review & editing. Chen Pan and Wen-qiong Ni are responsible for data curation, formal analysi and writing - original draft, Qu Xiao-yan is responsible for investigation and methodology, Xiao Hui is responsible for funding acquisition. All authors read and approved the final manuscript. Acknowledgement The authors thank AiMi Academic Services (www.aimieditor.com) for English language editing and review services. References Armstrong AW, Read C (2020) Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA 323:1945–1960. 10.1001/jama.2020.4006 Boehncke WH, Schön MP (2015) Psoriasis Lancet 386:983–994. 10.1016/S0140-6736(14)61909-7 Bonaventura A, Vecchié A, Abbate A, Montecucco F, Cells (2020) ;9. 10.3390/cells9010231 Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. 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For other variables (sex, clinical subtype, psoriatic arthritis, treatment), the P values were determined using Chi-square test and Fisher’s exact test. c For analysis of treatment, the numbers of patients who had or had not received a particular form of treatment were compared. Clinical parameter Low NET amount（n=31） a High NET amount（n=32） P value b Age 45.84±14.08 46.97±15.57 0.767 Sex 0.316 Male（n=42） 19 cases 23 cases Female（n=21） 7 cases 14 cases Clinical subtype 0.110 Psoriasis vulgaris (n= 39) 18 cases 21 cases Guttate psoriasis(n= 11) 7 4 Erythrodermic psoriasis (n= 5) 0 5 Pustular psoriasis（n=6） 2 4 Psoriatic arthritis 0.495 Yes（n=2） 0 2 No（n=61） 27 30 PASI score 18.03±1.28 23.69±1.42 ﹤0.01 Treatment c No treatment (n= 11) 4 7 0.545 Topical therapy (n=42 ) 20 22 0.722 Phototherapy (n= 32) 15 17 0.707 Methotrexate (n= 12) 5 7 0.561 Cyclosporine (n= 9) 3 6 0.504 Biological agent (n= 5) 3 2 0.970 Table 2 Comparative analysis table of positive rate and fluorescence intensity of NETs in peripheral blood of psoriasis patients and healthy controls Data name Psoriasis group Healthy control group P Statistical method Simple size（ n ） 63 27 — — Age（ x̄ ± s ） 40.68±12.44 39.33 ± 11.86 0.638 Mann-Whitney U test ( Z =-0.63, N =90) Gender（male/female） 42/21 15/12 0.32 χ 2 ( χ 2 =1.01, v =1) Score of PASI（ x̄ ± s ） 20.89 ± 8.00 — — — Score of BSA（ x̄ ± s ） 46.03 ± 21.27 — — — The positive rate of NETs（ x̄ ± s ） 15.57% ± 0.13% 8.35% ± 0.05% 0.002 ** t test ( t =3.15, v =88) Total fluorescence intensity（ x̄ ± s ） 768 525.39 ± 1 053 035.05 253 336.34 ± 214 072.32 0.000 ** t test ( t =4.58, v =88) Proportion of fluorescence（ x̄ ± s ） 26 989.00 ± 30 089.94 11 008.13 ± 7 375.58 0.000 ** t test ( t =4.62, v =88) Average fluorescence intensity（ x̄ ± s ） 25.79 ± 7.82 19.93 ± 7.20 0.001 ** t test ( t =3.33, v =88) Note: PASI：Psoriasis Area and Severity Index；BSA：Body Surface Area Table 3 Comparison of NETs expression among different psoriasis types Psoriasis vulgaris n =39 Guttate psoriasis n =11 Erythrodermic psoriasis n =5 Pustular psoriasis n =6 Psoriatic arthritis n =2 P The positive rate of NETs（ x̄ ） 0.15 0.22 0.13 0.13 0.05 0.46 Total fluorescence intensity（ x̄ ） 776 082.13 1 016 421.45 538 847.07 630 813.76 245 071.50 0.65 Proportion of fluorescence（ x̄ ） 26 610.53 36 694.83 21 663.83 21 913.36 9 526.90 0.55 Average fluorescence intensity（ x̄ ） 25.96 23.27 23.94 30.04 27.95 0.57 Table 4 Correlation analysis of laboratory indicators with NETs and disease severity in psoriasis group laboratory indicators Results Simple size[ n (%)] P PASI BSA Positive rate of NETs Total fluorescence intensity Proportion of fluorescence Average fluorescence intensity Metabolic indicators (blood glucose, blood lipids) abnormal /normal 23(47.92%)/25(52.08%) 0.85 0.81 0.35 0.34 0.03* 0.55 TNF-α abnormal /normal 20(47.62%)/22(52.38%) 0.20 0.13 0.33 0.01** 0.01** 0.33 IL-6 abnormal /normal 18(35.29%)/33(64.71%) 0.34 0.80 0.67 0.65 0.91 0.13 CRP abnormal /normal 18(29.51%)/43(70.49%) 0.47 0.39 0.07 0.79 0.68 0.08 PCT abnormal /normal 21(42.00%)/29(58.00%) 0.88 0.71 0.17 0.31 0.35 0.77 NLR ≥M /＜M 32(50.79%)/31(49.21%) 0.13 0.28 0.93 0.50 0.55 0.84 PLR ≥M/＜M 32(50.79%)/31(49.21%) 0.37 0.57 0.85 0.74 0.84 0.89 SII ≥M/＜M 32(50.79%)/31(49.21%) 0.60 0.75 0.58 0.89 0.93 0.86 dNLR ≥M/＜M 32(50.79%)/31(49.21%) 0.67 0.97 0.55 0.71 0.44 0.40 Note: M: median Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 10 Feb, 2026 Editor assigned by journal 21 Jan, 2026 Submission checks completed at journal 21 Jan, 2026 First submitted to journal 12 Jan, 2026 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8577940","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591739602,"identity":"f2bbfaea-86b3-4244-b323-9b26779c948a","order_by":0,"name":"Pan Chen","email":"","orcid":"","institution":"Zhengzhou University Affiliated Zhengzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pan","middleName":"","lastName":"Chen","suffix":""},{"id":591739603,"identity":"a29b5312-830e-4d7b-9050-cde3b3cc764d","order_by":1,"name":"Xiao-yan Qu","email":"","orcid":"","institution":"Zhengzhou University Affiliated Zhengzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiao-yan","middleName":"","lastName":"Qu","suffix":""},{"id":591739604,"identity":"26923e41-e926-416f-9155-e944ab2f5a20","order_by":2,"name":"Wen-qiong Ni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBACNmb2ww8SKmzk+NmbDxCnhY+9J83gwZk0Y8meYwnEaZHjOWAg+bDtcOKGGz4GRDpMIiHBIOHM4cSGGzwfb7xhsJPTbSCoJfEA0C/pxo2zezdbzmFINjY7QJwt1rLNMme3SfMwHEjcRoQWA4nENmbGNomcZ0RqAXofqMVZsUcih41ILaBATgAGsgTPMWPLOQZE+EW+mf3wwx/AqLQ/3vzwxpsKOzmCWlCABA+RUYOshVQdo2AUjIJRMCIAAFoiRUnT/IA0AAAAAElFTkSuQmCC","orcid":"","institution":"Zhengzhou University Affiliated Zhengzhou Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Wen-qiong","middleName":"","lastName":"Ni","suffix":""},{"id":591739605,"identity":"c6c6367a-ae73-4225-bdb7-a4badc737eb3","order_by":3,"name":"Hui Xiao","email":"","orcid":"","institution":"Zhengzhou University Affiliated Zhengzhou Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Xiao","suffix":""}],"badges":[],"createdAt":"2026-01-12 06:23:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8577940/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8577940/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102791109,"identity":"36907d81-aa25-4a5d-b027-e929375ea6d0","added_by":"auto","created_at":"2026-02-16 17:17:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":164597,"visible":true,"origin":"","legend":"\u003cp\u003eThe expression of NETs in psoriatic lesions Positive expression of H3Cit is seen in the Munro microabscess in the skin of a psoriatic patient. (A): 100× fluorescence microscope; (B) : HE staining 100× microscope\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8577940/v1/480ec68f8a799b5b77f43e9f.png"},{"id":102791110,"identity":"68fa839a-b3ba-48a6-886a-85ac700ab5a3","added_by":"auto","created_at":"2026-02-16 17:17:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":335124,"visible":true,"origin":"","legend":"\u003cp\u003eThe expression of NETs in psoriasis group and healthy control group\u003c/p\u003e\n\u003cp\u003e(A) : Comparison of 200× fluorescence microscopy psoriasis and healthy control NETs; (B) : 400× fluorescence microscopy of psoriatic NETs; (C) Quantitative analysis of NETs expression in healthy control and psoriasis groups\u003c/p\u003e\n\u003cp\u003eNote：H3Cit: Citrullinated histone 3, NETs specific protein; MPO: Myeloperoxidase, expressed in neutrophil cytoplasm and NETs; DNA: Constitutes the skeleton of neutrophil nuclei and NETs; Merge: Only MPO and DNA fluorescence, representing normal neutrophils, while fluorescence containing both H3Cit, MPO and DNA represents NETs.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8577940/v1/eb2939ceba1791063647e170.png"},{"id":102791111,"identity":"a686a208-86b7-4baa-8ba9-f406bf771094","added_by":"auto","created_at":"2026-02-16 17:17:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":66127,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of the correlation between the positive rate of NETs in psoriatic peripheral blood and the severity of disease\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8577940/v1/b9318bf7d07fdfc7ba6eef5f.png"},{"id":104397176,"identity":"35a1e99a-aaee-4a3a-a117-7b6cb9a9801e","added_by":"auto","created_at":"2026-03-11 11:40:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1401632,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8577940/v1/c4fe15c5-1e7a-46a2-829b-edeee603ca0e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eObservation on The Formation of Neutrophil Extracellular Traps in Psoriatic Peripheral Blood\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsoriasis is a common, chronic inflammatory skin disease with a high incidence that can occur in adults and children\u003csup\u003e[12]\u003c/sup\u003e. Generalized skin lesions throughout the body bring substantial economic and psychological burdens to individuals\u003csup\u003e[2]\u003c/sup\u003e. In addition to psoriasis, patients are more likely to have certain other systemic diseases, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, and autoimmune diseases, generally considered to be comorbidities of psoriasis\u003csup\u003e[14]\u003c/sup\u003e. However, the mechanism of psoriasis and its comorbidity is still unclear.Existing studies believe it is caused by genetic and environmental factors\u003csup\u003e[13]\u003c/sup\u003e. In addition, a variety of traditional immune cells like T cells, dendritic cells, and neutrophils, as well as non-traditional immune cells like keratinocytes, \u0026nbsp; contribute to the development of psoriasis. \u0026nbsp;Neutrophils, despite \u0026nbsp;their brief \u0026nbsp; lifespan, may also have a role in this process\u003csup\u003e[6]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eNeutrophils are attracted to areas of psoriasis, especially in the epidermis, where they come together to create Kogoj spongiform pustules in the stratum spinosum and Munro microabscesses in the stratum corneum\u003csup\u003e[30]\u003c/sup\u003e. The \u0026nbsp; exact \u0026nbsp;contribution of neutrophils to the development of psoriasis remains unclear, but \u0026nbsp;evidence from cases \u0026nbsp;of drug-induced agranulocytosis leading to improvement and subsequent relapses upon neutrophil count normalization indicates a significant \u0026nbsp;involvement \u0026nbsp;of neutrophils\u003csup\u003e[6]\u003c/sup\u003e. Additionally, neutrophils can take the lead in capturing exogenous stimuli such as bacteria and viruses and release neutrophil extracellular traps (NETs) through a unique death mechanism\u003csup\u003e[9]\u003c/sup\u003e. Brinkmann et al. described this mechanism in 2004: Histone 3(H3) citrullination modification uncoilates chromatin, eventually leading to the programmed externalization of grain-derived protein-modified chromatin fiber networks (NETs). This process is named NETosis\u003csup\u003e[4]\u003c/sup\u003e. In the process of NETosis, NETs serve as a natural biological defense mechanism, and their elevation is associated with inflammatory response and related diseases such as obesity, atherosclerosis, and cancer\u003csup\u003e[3,8]\u003c/sup\u003e. Moreover, it acts as an autoantigen associated with various autoimmune diseases\u003csup\u003e[25]\u003c/sup\u003e. The \u0026nbsp; exact \u0026nbsp;contribution of NETosis to the development of psoriasis remains uncertain at this \u0026nbsp;time.\u003c/p\u003e\n\u003cp\u003eThis research \u0026nbsp;examined the creation of NETs by neutrophils in the peripheral blood and skin sores of individuals with psoriasis, with or without metabolic syndrome, in comparison to individuals without any health \u0026nbsp;issues.In addition, \u0026nbsp;we examined the relationship between NETs and clinical categorization, severity of illness, and markers of inflammation in \u0026nbsp;order \u0026nbsp; to \u0026nbsp;offer insight \u0026nbsp;into the role of neutrophils in the development of psoriasis.Thus, these findings illustrate a novel mechanism by which NETs promote a sustained inflammatory response in pso\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1.1 Recruitment of patients.\u003c/strong\u003e\u0026nbsp; The Department of Dermatology at Zhengzhou University\u0026apos;s central hospital \u0026nbsp; enrolled \u0026nbsp;63 individuals diagnosed with psoriasis.Furthermore, 27 individuals without health issues were enlisted through advertising.Blood samples were collected from both patients and healthy individuals through peripheral veins.At the time of blood sampling, information \u0026nbsp;was gathered on the type of psoriasis, \u0026nbsp;the \u0026nbsp;existence of psoriatic arthritis, the severity of the disease, and the treatments used for psoriasis (such as topical therapy, phototherapy, immunosuppressive drugs, and biological agents).The severity of psoriasis in each patient was assessed by the PASI score and BSA, which measures the seriousness of skin lesions and the extent of the affected area.Approval for the study was granted by the ethics committee at Zhengzhou University Affiliated Zhengzhou Central Hospital, and the \u0026nbsp;research was carried out in \u0026nbsp;compliance with the Declaration of Helsinki.All patients and healthy controls provided written informed \u0026nbsp;consent before participating in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.2 Isolation of peripheral blood neutrophils.\u0026nbsp;\u003c/strong\u003eNeutrophils from peripheral blood were separated using centrifugation with a density gradient.Histopaque-1119 (11191) and Histopaque-1077 (10771) were bought from Sigma-Aldrich, while red blood cell lysate (R1010) was bought from Beijing Solaibao Technology Co., LTD. A mixture of Histopaque-1119 4mL, Histopaque-1077 2mL, and fresh peripheral blood 2mL (collected within 1 hour) \u0026nbsp;was \u0026nbsp; gently added to a 15 ml centrifuge tube, then centrifuged at 700g for 30 \u0026nbsp;minutes at room temperature.Plasma layer from top to bottom, respectively, a single nuclear cell layer, layer, neutrophils, Histopaque Histopaque - 1077-1119, the red blood cells layer.With aseptic suction drain neutrophils layer cell suspension, PBS washing, again after red blood cell cracking liquid soluble red treatment for immunofluorescence staining.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.3 Visual quantification of NETosis by fluorescence microscopy.\u0026nbsp;\u003c/strong\u003eThe formation of NETs was observed by immunofluorescence staining.Neutrophils from human peripheral blood were cultured in complete medium (CM - H197) obtained from Wuhan Puno Life Technology Co., Ltd. The cells were supplemented \u0026nbsp;with closed goat serum (SL038) from Mr. Lai Treasure Technology Co., Ltd. \u0026nbsp; Additionally, \u0026nbsp;a rabbit anti-histone H3 (citrulline R2 + R8 + R17) polyclonal antibody (ab5103), a murine anti-MPO monoclonal antibody (ab25989), ALexarFluor 488-labeled goat anti-rabbit IgG secondary antibody (ab150077), and ALexarFluor 594 labeled goat anti-mouse IgG secondary antibody (ab150116) were all purchased from Abcam.Fluorescence quenching sealing tablet (DAPI) resistance (P0131) purchased from Beijing blue skies biotechnology co., LTD.Isolate fresh neutrophils from peripheral blood, \u0026nbsp;suspend in complete medium, adjust cell density to 100 x 104 / mL, seed cells \u0026nbsp;onto \u0026nbsp; 6-well plates coated \u0026nbsp;with poly \u0026nbsp;lysine, add 200 ul of cell suspension \u0026nbsp;to \u0026nbsp; each \u0026nbsp;well, \u0026nbsp;incubate \u0026nbsp; for 1 hour, fix with 4% formaldehyde for 20 minutes, permeabilize with 0.2% Triton X-100 for 10 minutes, \u0026nbsp;block with goat serum for \u0026nbsp;1 hour, incubate with \u0026nbsp;antibodies \u0026nbsp;against H3Cit and MPO overnight at \u0026nbsp;4 \u0026nbsp;℃, wash with PBS, incubate with fluorescent secondary antibodies at room temperature for 1 hour in the dark.After washing three times with PBS again, the slides were sealed with anti-fluorescence quenching mounting solution containing DAPI, and then observed under a fluorescence microscope.Images were taken using Image View software, and fluorescence image analysis was performed using ImageJ software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.6 Immunofluorescence staining.\u003c/strong\u003e After fixing the cells with a 4% formaldehyde solution, they were then washed with PBS.Subsequently, the cells were treated with a 0.5% solution of octylphenol polyethylene glycol ether for 20 \u0026nbsp;minutes at ambient temperature, followed by \u0026nbsp;a PBS rinse.The cells were blocked with 5%BSA solution for 30min at room temperature.The initial antibody was prepped and then \u0026nbsp; applied to every slide in the sealed well plate, followed by \u0026nbsp;an \u0026nbsp; overnight incubation at 4℃.After that, the slides were submerged in a PBST solution and left to interact with the secondary antibody for 1 hour at room temperature in darkness.DAPI staining solution was added for 5min.Finally, it was observed under the microscope.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.7 Statistical analysis.\u003c/strong\u003e GraphPad Prism 7 software was \u0026nbsp;utilized for all statistical analyses, with \u0026nbsp;error \u0026nbsp;bars \u0026nbsp; representing standard error of \u0026nbsp; the mean (s.e.m).or s.d.The figure \u0026nbsp; legends \u0026nbsp;provide details on the number of trials, \u0026nbsp;occurrences, and statistical methods used in each independent experiment.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e3.1.1 Clinical features of patients.\u003c/strong\u003e Characteristics of individuals in a \u0026nbsp;clinical setting.63 patients \u0026nbsp;with psoriasis were examined in this research, where \u0026nbsp;we studied neutrophils in \u0026nbsp;peripheral \u0026nbsp;blood \u0026nbsp; and \u0026nbsp;sera.The average age of individuals with psoriasis was 40.68 years, with a standard deviation of 12.44.There were 42 males and 21 females \u003cstrong\u003e\u003cem\u003e(Table 1)\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e.\u003c/em\u003e The clinical subtype was psoriasis vulgaris in 39 cases, guttate psoriasis in 11 cases, erythrodermic psoriasis in 5 cases， pustular psoriasis in 6 cases, and articular psoriasis in 2 cases.In 4 instances, the Psoriasis Area and Severity Index (PASI) rating was less than 10, \u0026nbsp; while \u0026nbsp;it \u0026nbsp;fell between 10 and 20 in 22 cases, 20 and 30 in 29 cases, and 30 and 40 in 8 cases.Treatment \u0026nbsp; options for psoriasis patients at the time of blood sampling included no treatment (11 patients), topical therapy (42 patients \u0026nbsp;with topical steroids, vitamin D analogs, and retinoids), ultraviolet light phototherapy (32 patients), methotrexate (12 patients), cyclosporine (9 patients), and secukinumab \u0026nbsp;(5 patients).Additionally, we incorporated 27 individuals without health issues in our research, with \u0026nbsp;an \u0026nbsp; average age of 39.33 years and a standard deviation of 11.86 years, consisting of 15 men and 12 women.Notably, there was no statistically significant difference in age between psoriasis patients and healthy controls (\u003cem\u003eP\u003c/em\u003e =0.638).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.2 Formation of NETs in skin lesions of psoriasis\u003c/strong\u003e NETs \u0026nbsp;formation was \u0026nbsp;detected in psoriasis skin \u0026nbsp;lesions using \u0026nbsp; a fluorescence microscope.The results showed that positive expression of H3Cit was observed in Munro micro-abscess of skin lesions from psoriasis patients\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(Figure 1)\u003c/em\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.3 A comparison of spontaneous NETs in peripheral blood between the psoriasis and healthy control groups.\u003c/strong\u003e The morphology and number of NETs were observed under a fluorescence microscope, and the visual fields were randomly selected under 200 \u0026times; magnification for each sample.ImageJ software was used to analyze the fluorescence intensity and semi-quantitative count.The number of H3Cit (+) cells/DNA (+) cells in each field of view was used as the positive rate of NETs, and the green fluorescence of H3Cit represented the fluorescence intensity and area of NETs.The findings indicated a \u0026nbsp;higher positivity rate of NETs, total fluorescence intensity, average fluorescence intensity, and fluorescence area of H3Cit in the peripheral blood of psoriasis patients compared \u0026nbsp;to the healthy control group.Similarly, there was a statistically significant variation (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01) \u003cstrong\u003e\u003cem\u003e(Figure 2, Table 2).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.4 The severity of psoriasis is directly related to the positivity rate of NETs.\u003c/strong\u003e To understand the possibility of NETs as a clinical indication of psoriasis, we evaluated the correlation between the development of NETs and the severity of psoriasis.A Pearson\u0026apos;s test was used to analyze the correlation between the positive rate of NETs and PASI and BSA scores.The findings were as follows: The presence of NETs in peripheral blood was directly associated with the severity of psoriasis as measured by the PASI score (r=0.31, \u003cem\u003eP\u003c/em\u003e=0.013). However, these were not significantly correlated with the BSA score (r=0.17, \u003cem\u003eP\u003c/em\u003e=0.175) (\u003cstrong\u003e\u003cem\u003eFigure 3\u003c/em\u003e\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.5 Comparative analysis of spontaneous NETs among different types of psoriasis.\u0026nbsp;\u003c/strong\u003eTo understand the relationship between the formation of NETs and the classification of psoriasis, we compared the formation of NETs in different types of psoriasis.The findings indicated that there were no notable \u0026nbsp;variances in the positivity rate, overall brightness level, fluorescence distribution, and mean \u0026nbsp;brightness level of NETs across the various psoriasis categories (Kruskal-Wallis Test was used for multiple group comparison, Mann-Whitney U test was used for comparison between the two groups, \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05; \u003cstrong\u003e\u003cem\u003eTable 3\u003c/em\u003e\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.6 Correlation analysis between peripheral blood NETs and laboratory results of psoriasis.\u0026nbsp;\u003c/strong\u003eRetrospectively, \u0026nbsp;we gathered clinical data including blood glucose, blood lipid, blood uric acid, Tumor Necrosis Factor-\u0026alpha; (TNF-\u0026alpha;), Interleukin-6 (IL-6), C-reaction protein (CRP), and Procalcitonin (PCT).The psoriasis group was divided into a normal result group and an abnormal result group.PASI, BSA, and spontaneous NETs between the two groups were analyzed.The fluorescence area of NETs in the group with metabolic abnormalities was notably greater compared \u0026nbsp;to the group without metabolic abnormalities, with statistical significance (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). Moreover, the combined fluorescence intensity and area of NETs in the high TNF-\u0026alpha; category were notably greater compared to the normal TNF-\u0026alpha; group (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05).No notable variations were observed in the positivity rate of NETs, the ratio of fluorescence, overall fluorescence strength, mean fluorescence strength, PASI, and BSA ratings between the elevated IL-6, CRP, and PCT categories, and the standard IL-6, CRP, and PCT categories (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05) (\u003cstrong\u003e\u003cem\u003eTable 4\u003c/em\u003e\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eGenetic and environmental factors are closely related to the pathogenesis of psoriasis\u003csup\u003e[19]\u003c/sup\u003e. In the interplay between genetic susceptibility and environmental triggers, infection related to microbiota invasion may be a key player\u003csup\u003e[26]\u003c/sup\u003e. Neutrophils, as immune cells in the early response to infection, play a role after receiving stimulation from microorganisms related to the inflammatory immune response in psoriasis\u003csup\u003e[5]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eNeutrophils are \u0026nbsp;crucial in the development of psoriasis.As a \u0026quot;pioneer soldier\u0026quot; in the innate immune response, it can transform into NETs through phagocytosis, degranulation, or activation to participate in the immune response\u003csup\u003e[18]\u003c/sup\u003e. Studies have shown that the depletion of neutrophils can alleviate psoriasis-like skin lesions in psoriasis-like mouse models\u003csup\u003e[28]\u003c/sup\u003e. Notably, psoriatic lesions improve in patients with drug-induced agranulocytosis, while psoriasis recurs after normalization of neutrophil counts\u003csup\u003e[31]\u003c/sup\u003e. Moreover, some studies have found that the content of NETs in skin lesions of patients with psoriasis is significantly increased\u003csup\u003e[24]\u003c/sup\u003e. In a \u0026nbsp;mouse model of psoriasis induced \u0026nbsp;by imiquimod, the continuous intravenous administration of CI-amide for a week (which decreased the production of NETs) led to a significant \u0026nbsp;decrease in the levels of NETs in the bloodstream, the infiltration of T cells and neutrophils in the dermis, and the release of inflammatory mediators in skin cells.Reducing the release of NETs can \u0026nbsp;greatly alleviate \u0026nbsp;psoriasis by significantly decreasing the \u0026nbsp;hypertrophy of the scale \u0026nbsp;and spinous layer of the \u0026nbsp;back skin \u0026nbsp; in \u0026nbsp;mice\u003csup\u003e[29]\u003c/sup\u003e. The \u0026nbsp; research \u0026nbsp;discovered a \u0026nbsp;rise in NETs formation in the bloodstream \u0026nbsp;of psoriasis patients, \u0026nbsp;which was linked \u0026nbsp;to \u0026nbsp; higher PASI scores, indicating a potential role of neutrophils in the development of psoriasis through NETs formation.However, the specific mechanism is still unclear.Existing studies have found that NETs can promote a large number of non-activated neutrophils to chemotaxis, migration to the epidermis, and further secretion of NETs, forming a self-amplifying immune activation cycle based on repeated activation of neutrophils\u003csup\u003e[15]\u003c/sup\u003e. In this cycle, the continuously released NETs activate PDCS, stimulate keratinocytes, and interact with Th17 to release many chemokines and inflammatory mediators, ultimately leading to psoriasis occurrence and development.Therefore, detecting NETosis cells in peripheral blood may be used as an inflammatory indicator to evaluate the condition of patients with psoriasis or provide a basis for treating targeted neutrophils.\u003c/p\u003e\n\u003cp\u003eThe current research also identified a connection between serum TNF-\u0026alpha; levels and NETs in individuals diagnosed with psoriasis.This correlation has also been reported in rheumatoid arthritis31 and radiation-induced axial spondylarthritis\u003csup\u003e[27]\u003c/sup\u003e.\u0026nbsp;The latter found reduced NETosis production after infliximab (a TNF-\u0026alpha; inhibitor) treatment.Other studies have found that in patients with rheumatoid arthritis, infliximab treatment can inhibit the formation of NETs, reduce the production of inflammatory mediators, and improve disease activity\u003csup\u003e[7]\u003c/sup\u003e. These results suggest that TNF-\u0026alpha; may promote the formation of NETs, and NETs may be one of the indicators for evaluating the efficacy of TNF-\u0026alpha; monoclonal antibody in treating psoriasis.\u003c/p\u003e\n\u003cp\u003eRecent research has \u0026nbsp;shown a strong \u0026nbsp;connection \u0026nbsp; between the production of NETs and the development of different non-infectious acute and chronic illnesses in recent years\u003csup\u003e[16]\u003c/sup\u003e. Environmental factors such as microbial infection, stress, smoking, obesity, and alcohol consumption, as the critical risk factors and triggers of psoriasis, have systemic effects on the body\u003csup\u003e[1]\u003c/sup\u003e.\u0026nbsp;Therefore, psoriasis is often co-morbid with other diseases and added clinical studies have confirmed that psoriasis is often combined with metabolism-related diseases\u003csup\u003e[21]\u003c/sup\u003e. Metabolic syndrome has been proposed to \u0026nbsp;elevate the likelihood of cardiovascular disease and early \u0026nbsp; mortality in individuals with psoriasis, leading to a \u0026nbsp;notable \u0026nbsp; decrease in their lifespan\u003csup\u003e[11]\u003c/sup\u003e. Long-term metabolic disorders in these comorbidities can cause long-term activation of innate immunity, resulting in long-lasting metabolic inflammation\u003csup\u003e[20]\u003c/sup\u003e. Likewise, the oxidative stress environment and inflammatory factors produced by inflammatory cells provide a favorable microenvironment for the process of NETosis, causing psoriasis recurrence under the influence of a trigger factor\u003csup\u003e[17]\u003c/sup\u003e. Furthermore, research has indicated a \u0026nbsp;notable rise \u0026nbsp; in the creation of NETs in \u0026nbsp; individuals \u0026nbsp;with type 2 diabetes mellitus and the \u0026nbsp;related atherosclerosis. ApoE\u003csup\u003e-/-\u003c/sup\u003e mice that suppress NETosis by eliminating NE and protease-3 exhibit significantly decreased AS lesions in comparison \u0026nbsp;to ApoE\u003csup\u003e-/-\u003c/sup\u003e knockout mice\u003csup\u003e[22]\u003c/sup\u003e. Subjects with metabolic syndrome and type 1 diabetes were treated with Secukinumab (an effective biological agent for treating plaque psoriasis).The average body weight, waist circumference, and BMI of those who responded positively decreased in comparison to the control group\u003csup\u003e[10]\u003c/sup\u003e. These findings suggest that NETs are closely associated with psoriasis and its metabolism-related comorbidities.This study showed that patients with psoriasis and metabolic abnormalities had increased spontaneous NETs compared to those without.Furthermore, NETs may be one of the mechanisms linking psoriasis and its comorbidities.Notably, drugs targeting neutrophils, especially NETs, may become one of the therapeutic targets for psoriasis.Dimethyl fumarate, a therapeutic drug for psoriasis, can weaken the function of neutrophils and inhibit the formation of NETs, which corroborates the possibility of NETs as a therapeutic target for psoriasis\u003csup\u003e[23]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAcute infection is a key factor in psoriasis\u0026apos;s trigger and relapse mechanism, and neutrophils are the \u0026quot;seeds\u0026quot; of the early response to acute infection.The inflammatory state in patients with metabolic disorders provides \u0026quot;fertile soil\u0026quot; for this process, promoting neutrophil NETosis to release NETs.Furthermore, the inflammatory immune reaction \u0026nbsp;quickly spreads and intensifies, ultimately resulting in the onset, progression, and reappearance of psoriasis.However, the specific mechanism of this process still needs further exploration and research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe corresponding author is responsible for data curation, supervision and writing - review \u0026amp; editing. Chen Pan and Wen-qiong Ni are responsible for data curation, formal analysi and writing - original draft, Qu Xiao-yan is responsible for investigation and methodology, Xiao Hui is responsible for funding acquisition. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank AiMi Academic Services (www.aimieditor.com) for English language editing and review services.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eArmstrong AW, Read C (2020) Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. 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Front Immunol ;10:746. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2019.00746\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2019.00746\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. eCollection 2019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakahashi T, Yamasaki K (2020) Psoriasis and Antimicrobial Peptides. Int J Mol Sci ;21\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToichi E, Tachibana T, Furukawa F (2000) Rapid improvement of psoriasis vulgaris during drug-induced agranulocytosis. J Am Acad Dermatol 43:391\u0026ndash;395. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1067/mjd.2000.103264\u003c/span\u003e\u003cspan address=\"10.1067/mjd.2000.103264\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Association between amount of NETotic cells in the peripheral blood (low versus high NET amount) and clinical parameters in patients with psoriasis (n=63). \u0026nbsp;\u003csup\u003ea\u003c/sup\u003ePatients with psoriasis were categorized into the low NET amount group or high NET amount group using the mean amount of NETotic cells in the peripheral blood as the dividing point. \u003csup\u003eb\u003c/sup\u003eThe P values for age and PASI score were determined using the two sample t-test. \u0026nbsp;For other variables (sex, clinical subtype, psoriatic arthritis, treatment), the P values were determined using Chi-square test and Fisher\u0026rsquo;s exact test. \u0026nbsp; \u003csup\u003ec\u003c/sup\u003eFor analysis of treatment, the numbers of patients who had or had not received a particular form of treatment were compared.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eClinical parameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eLow NET amount（n=31）\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHigh NET amount（n=32）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e45.84\u0026plusmn;14.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e46.97\u0026plusmn;15.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eMale（n=42）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e19 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e23 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eFemale（n=21）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e14 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eClinical subtype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003ePsoriasis vulgaris (n= 39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e21 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eGuttate psoriasis(n= 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eErythrodermic psoriasis (n= 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003ePustular psoriasis（n=6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003ePsoriatic arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eYes（n=2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eNo（n=61）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003ePASI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18.03\u0026plusmn;1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e23.69\u0026plusmn;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e﹤0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eTreatment\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eNo treatment (n= 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.545\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eTopical therapy (n=42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.722\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003ePhototherapy (n= 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.707\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eMethotrexate (n= 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eCyclosporine (n= 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eBiological agent (n= 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.970\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 Comparative analysis table of positive rate and fluorescence intensity of NETs in peripheral blood of psoriasis patients and healthy controls\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eData name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003ePsoriasis group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eHealthy control group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eStatistical method\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eSimple size（\u003cem\u003en\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eAge（\u003cem\u003ex̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e40.68\u0026plusmn;12.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e39.33 \u0026plusmn; 11.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.638\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003eMann-Whitney U test\u0026nbsp;\u003c/em\u003e(\u003cem\u003eZ\u003c/em\u003e=-0.63, \u003cem\u003eN\u003c/em\u003e=90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eGender（male/female）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e42/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e15/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e(\u003cem\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=1.01, \u003cem\u003ev\u003c/em\u003e=1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eScore of PASI（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e20.89\u003cem\u003e\u0026plusmn;\u003c/em\u003e8.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eScore of BSA（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e46.03\u003cem\u003e\u0026plusmn;\u003c/em\u003e21.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eThe positive rate of \u0026nbsp;NETs（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e15.57%\u003cem\u003e\u0026plusmn;\u003c/em\u003e0.13%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e8.35%\u003cem\u003e\u0026plusmn;\u003c/em\u003e0.05%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.002\u003csup\u003e**\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e\u003cem\u003etest\u0026nbsp;\u003c/em\u003e(\u003cem\u003et\u003c/em\u003e =3.15, \u003cem\u003ev\u003c/em\u003e=88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eTotal fluorescence intensity（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e768 525.39\u003cem\u003e\u0026plusmn;\u003c/em\u003e1 053 035.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e253 336.34\u003cem\u003e\u0026plusmn;\u003c/em\u003e214 072.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.000\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e\u003cem\u003etest\u0026nbsp;\u003c/em\u003e(\u003cem\u003et\u003c/em\u003e =4.58, \u003cem\u003ev\u003c/em\u003e=88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eProportion of fluorescence（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e26 989.00\u003cem\u003e\u0026plusmn;\u003c/em\u003e30 089.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e11 008.13\u003cem\u003e\u0026plusmn;\u003c/em\u003e7 375.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.000\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e\u003cem\u003etest\u0026nbsp;\u003c/em\u003e(\u003cem\u003et\u003c/em\u003e =4.62, \u003cem\u003ev\u003c/em\u003e=88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003eAverage fluorescence intensity（\u003cem\u003e\u0026nbsp;x̄\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u003c/em\u003e\u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e25.79\u003cem\u003e\u0026plusmn;\u003c/em\u003e7.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e19.93\u003cem\u003e\u0026plusmn;\u003c/em\u003e7.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cem\u003et\u0026nbsp;\u003c/em\u003e\u003cem\u003etest\u0026nbsp;\u003c/em\u003e(\u003cem\u003et\u003c/em\u003e =3.33, \u003cem\u003ev\u003c/em\u003e=88)\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\u003eNote: PASI：Psoriasis Area and Severity Index；BSA：Body Surface Area\u003c/p\u003e\n\u003cp\u003eTable 3 Comparison of NETs expression among different psoriasis types\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"715\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003ePsoriasis vulgaris\u003cbr\u003e\u003cem\u003en\u003c/em\u003e=39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eGuttate psoriasis\u003cbr\u003e\u003cem\u003en\u003c/em\u003e=11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eErythrodermic psoriasis\u003cbr\u003e\u003cem\u003en\u003c/em\u003e=5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003ePustular psoriasis\u003cbr\u003e\u003cem\u003en\u003c/em\u003e=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003ePsoriatic arthritis\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e=2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eThe positive rate of \u0026nbsp;NETs（\u003cem\u003ex̄\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eTotal fluorescence intensity（\u003cem\u003ex̄\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e776 082.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 016 421.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e538 847.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e630 813.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 112px;\"\u003e\n \u003cp\u003e245 071.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eProportion of fluorescence（\u003cem\u003ex̄\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e26 610.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e36 694.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e21 663.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e21 913.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 112px;\"\u003e\n \u003cp\u003e9 526.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eAverage fluorescence intensity（\u003cem\u003ex̄\u003c/em\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e25.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e23.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e23.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e30.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 112px;\"\u003e\n \u003cp\u003e27.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.57\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\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 Correlation analysis of laboratory indicators with NETs and disease severity in psoriasis group\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"722\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003elaboratory indicators\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 63px;\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 153px;\"\u003e\n \u003cp\u003eSimple size[\u003cem\u003en\u003c/em\u003e(%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width: 425px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003ePASI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eBSA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003ePositive rate of NETs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003eTotal fluorescence intensity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eProportion of fluorescence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003eAverage fluorescence intensity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eMetabolic indicators (blood glucose, blood lipids)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eabnormal /normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e23(47.92%)/25(52.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eTNF-\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eabnormal /normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e20(47.62%)/22(52.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.01**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.01**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eabnormal /normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e18(35.29%)/33(64.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eabnormal /normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e18(29.51%)/43(70.49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.07\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003ePCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eabnormal /normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e21(42.00%)/29(58.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026ge;M /＜M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e32(50.79%)/31(49.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003ePLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026ge;M/＜M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e32(50.79%)/31(49.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eSII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026ge;M/＜M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e32(50.79%)/31(49.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003edNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026ge;M/＜M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e32(50.79%)/31(49.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\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\u003eNote: M: median\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Psoriasis, metabolic syndrome, Neutrophil Extracellular Traps","lastPublishedDoi":"10.21203/rs.3.rs-8577940/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8577940/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo explore the clinical application value of Neutrophil extracellular traps (NETs) in evaluating psoriasis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e2ml peripheral blood of 63 patients with psoriasis and 27 healthy controls were collected. Neutrophils were isolated by density gradient method, and the formation of NETs was observed by immunofluorescence staining. We then calculated the proportion and fluorescence intensity of NETs and analyzed their correlation with clinical classification, severity, and serological indicators. Furthermore, the skin lesions of 5 patients with psoriasis were collected, and the NETs were observed by immunofluorescence method.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe proportion and fluorescence intensity of spontaneous NETs in patients with psoriasis were significantly higher than those in healthy controls and were positively correlated with the PASI scores. The generation of NETs in psoriasis patients with metabolic syndrome (MetS) or high-TNF-α was higher than in psoriasis patients without metabolic abnormalities or normal-TNF-α. NETs were also observed in most psoriatic skin specimens.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe levels of NETs are correlated with the disease severity of psoriasis and patients with metabolic abnormalities and may be used as a clinical indicator to reflect the inflammatory state of psoriasis and metabolic comorbidity of psoriasis for disease evaluation.\u003c/p\u003e","manuscriptTitle":"Observation on The Formation of Neutrophil Extracellular Traps in Psoriatic Peripheral Blood","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 17:17:36","doi":"10.21203/rs.3.rs-8577940/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-02-10T19:44:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-21T09:07:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-21T09:05:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2026-01-12T06:17:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9c31402a-5e6b-4340-a91c-61edd1048cf4","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T17:17:36+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 17:17:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8577940","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8577940","identity":"rs-8577940","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}