The relationship between serum taurine and disease activity indices in rheumatoid arthritis patients

The relationship between serum taurine and disease activity indices in rheumatoid arthritis patients | 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 The relationship between serum taurine and disease activity indices in rheumatoid arthritis patients Tuncer Şak, Mustafa Gür, Duygu Şak, Pınar Öner This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6893961/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The anti-inflammatory properties of taurine have been described in the literature. This study aims to investigate the relationship between serum taurine levels, inflammatory markers, and composite disease activity indices in patients with rheumatoid arthritis (RA). Methods A prospective single-center case‒control study was conducted between August 2024 and April 2025 at Elazığ Fethi Sekin City Hospital. Patients diagnosed with RA on the basis of the 2010 ACR/EULAR criteria and varying disease activity levels (according to the DAS28-ESR, DAS28-CRP, CDAI, and SDAI) were enrolled. The control group consisted of individuals without inflammatory rheumatic diseases confirmed by clinical, laboratory, and/or imaging evaluation. Serum taurine levels were measured from blood samples obtained after clinical assessment and analyzed alongside inflammatory markers and disease activity scores. Results Fifty-seven RA patients and 23 noninflammatory controls were included. Compared with controls, RA patients had significantly greater ESR, CRP, phGlobal, and HAQ-DI scores (all p < 0.01). However, the serum taurine levels did not differ significantly between the groups (94.55 pg/ml vs. 76.89 pg/ml, p = 0.361). In all the participants, taurine levels were negatively correlated with the DAS28-ESR (r = -0.271, p = 0.041). Among RA patients, taurine was negatively correlated with phGlobal (r = -0.268, p = 0.044) and the DAS28-ESR. A negative correlation with DAS28-CRP was observed but did not reach statistical significance (r = -0.253, p = 0.058). Conclusion Low serum taurine levels may be associated with increased RA disease activity, particularly as assessed by the DAS28-ESR. These findings suggest a potential role for taurine in RA pathophysiology and highlight the need for larger-scale studies to explore its therapeutic implications. Clinical trial number: Not applicaple. Rheumatoid arthritis taurine rheumatoid arthritis biomarker taurine supplementation Background Taurine (also known as 2-aminoethanesulfonic acid) is a sulfur-containing semiessential amino acid found in various tissues, including the brain, kidney, liver, and skeletal muscles. While it can be synthesized in the liver, kidney, and, to a lesser extent, in the brain via the cysteine sulfinate and transsulfuration pathways, dietary intake is necessary. Taurine-rich foods include meat, fish, poultry, and dairy products [ 1 – 5 ]. In addition to its role in various metabolic pathways, such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation, and membrane stabilization, the anti-inflammatory effects of taurine have also been reported in multiple studies [ 6 – 8 ]. The anti-inflammatory effects of taurine may occur through several mechanisms. Its antioxidant properties include modulation of mitochondrial respiratory chain subunit translation [ 9 , 10 ]; detoxification of hydrogen peroxide (H₂O₂), superoxide anion (O₂⁻), hydroxyl radicals (OH), and nitric oxide (NO) [ 11 , 12 ]; reduction in lipid peroxidation [ 13 , 14 ]; and membrane stabilization [ 15 , 16 ]. Additionally, the inhibition of mitogen-activated protein kinase (MAPK) activation and the suppression of proinflammatory cytokine expression play important roles in its anti-inflammatory effects [ 17 ]. Several in vitro, animal, and limited human studies have investigated the inhibition of proinflammatory cytokine expression by taurine. Kontny et al. demonstrated, via fibroblast-like synoviocytes (FLSs) obtained from rheumatoid arthritis (RA) patients, that taurine haloamines—taurine chloramine (Tau-Cl) and taurine bromamine (Tau-Br)—inhibit the production of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and prostaglandin E₂ (PGE₂), as well as cell proliferation, in a dose-dependent manner [ 18 – 20 ]. Chorazy et al. reported that Tau-Cl inhibited the production of interleukin-1β (IL-1β) and IL-6 and, at relatively high concentrations, tumor necrosis factor alpha (TNF-α) in peripheral blood mononuclear cells stimulated with bacterial lipopolysaccharides from healthy volunteers [ 21 ]. Similarly, Tau-Cl, Tau-Br, and carbon monoxide (CO) were shown to inhibit TNF-α, IL-6, and interleukin-12 (IL-12) production in a dose-dependent manner, while Tau-Cl was also found to inhibit matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) via different pathways [ 22 , 23 ]. Metabolomic profile analyses have revealed elevated taurine levels and activation of taurine metabolic pathways in the serum and synovial fluid of RA patients [ 24 , 25 ]. However, studies investigating treatment response prediction in RA patients have produced conflicting results. For example, Gosselt et al. reported that baseline plasma taurine levels were lower in early RA patients who did not respond to methotrexate (MTX) [ 26 ]. In contrast, Takahashi et al. reported lower mean taurine levels in patients who responded to TNF inhibitors [ 27 ]. In this study, we aimed to investigate whether there is a correlation between serum taurine levels and disease characteristics, inflammatory markers, and composite activity scales in patients with RA. Methods A prospective single-center case‒control study was conducted between August 2024 and April 2025. All participants were selected from patients admitted to the rheumatology clinics at Elazığ Fethi Sekin City Hospital. Patients who were diagnosed with RA according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis classification criteria were included. Disease activity was assessed via the Disease Activity Score (DAS) 28-Erythrocyte Sedimentation Rate (ESR), DAS 28-C Reactive Protein (CRP), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Patients with no inflammatory rheumatic pathology detected through clinical, laboratory, and/or imaging evaluations were included in the control group. Additionally, patients’ age, sex, disease duration, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels, medications, number of tender and swollen joints, hand and wrist involvement, patient and physician global assessment (pGlobal and phGlobal) scores, ESR and CRP levels, and health assessment questionnaire - disability index (HAQ-DI) scores were recorded. Patients aged 18 years and older who provided informed consent were included in the study. The included patients included those diagnosed with RA, newly diagnosed RA patients, and individuals without any signs of inflammatory rheumatic disease. Patients with additional inflammatory diseases, those receiving systemic immunosuppressive and/or corticosteroid treatment for other reasons, those showing signs of infection during evaluation, and pregnant patients were excluded. Blood samples were collected from both the patient and control groups after a 12-hour fasting period in tubes containing aprotinin (BD Vacutainer SST II Advance, BD, Plymouth, UK). The samples were centrifuged at 2000–3000 rpm for 20 minutes, and the plasma was aliquoted into small-volume tubes for storage and analysis. All the plasma samples were stored at − 20°C until the day of the assay. Plasma taurine levels were measured via a Human Taurine ELISA Kit (catalog no: SL3146Hu, SUNLONG BIOTECH, China) following the manufacturer’s instructions. The absorbance was measured with a Chromate 4300 microplate reader (Awareness Technology, Palm City, USA). The detection limit of the assay for taurine was 5 pg/mL. The intra-assay and interassay coefficients of variation for plasma taurine were < 10% and < 12%, respectively. Data analysis was performed via SPSS version 22.0 (Statistical Package for the Social Sciences). Descriptive statistics, including the mean, standard deviation, minimum, and maximum values, were calculated to summarize the variables’ basic characteristics. Categorical variables are presented as frequencies (n) and percentages (%). Independent samples t tests were used for group comparisons when parametric assumptions were met, and chi-square tests were used for categorical variables. Pearson correlation analyses were conducted to determine relationships between variables. A significance level of p < 0.05 was considered for all analyses. Data normality and suitability for parametric tests were assessed before analysis. The results are presented in tables with the indicated statistical significance levels. Results Table 1 summarizes the descriptive characteristics of the study participants. In the case group, 38.6% (n=22) were male, and 61.4% (n=35) were female, whereas in the control group, 39.1% (n=9) were male, and 60.9% (n=14) were female. Overall, 38.8% of the participants were male, and 61.3% were female. There was no significant difference in sex distribution between the groups (χ² = 0.002, p = 0.580). The mean age was 50.82 years (SD = 13.81) in the case group and 48.39 years (SD = 12.15) in the control group. The age difference was not statistically significant (t = 0.737, p = 0.463). Thus, the case and control groups were comparable in terms of age and sex. According to the analysis comparing the case and control groups in terms of selected biochemical and clinical parameters, no significant difference was found pGlobal and serum taurine levels (Table 2). Table 2. Clinical and biochemical parameters of the case and control groups Case (n=57) Control (n=23) t Sd p Mean Ss Mean Ss RF (IU/ml) 74.740 104.137 6.260 8.874 3.137 78 0.000 Anti CCP (IU/ml) 111.050 77.394 0.220 0.422 6.842 78 0.000 pGlobal (0-100) 50.530 27.866 43.480 31.853 0.982 78 0.329 phGlobal (0-100) 42.980 29.998 11.300 6.944 4.993 78 0.000 ESR (mm/h) 18.140 14.377 7.650 6.176 3.365 78 0.000 CRP (mg/dl) 14.051 23.033 4.909 4.518 1.882 78 0.006 HAQ-DI 1.055 0.707 0.549 0.533 3.091 78 0.003 Serum taurine (pg/ml) 94.554 87.916 76.887 42.377 0.919 78 0.361 Independent groups T- test When the characteristics of the case group were examined, it was seen that the mean disease duration was 7.89 (Sd=9,15) years, and the patient group could be grouped as having low disease activity based on DAS 28-ESR and DAS 28-CRP while could be grouped as moderate disease activity based on other scales (Table 3). Table 3. Patient characteristics of the case group N Mean Sd Min. Max. Disease duration (year) 57 7.890 9.149 0.000 38.000 DAS 28-ESR 57 3.313 1.490 0.630 6.310 DAS 28-CRP 57 3.248 1.316 1.180 6.320 SDAI 57 13.989 11.039 0.100 47.200 CDAI 57 12.528 9.549 0.000 37.000 TJC 57 2.250 3.297 0.000 16.000 SJC 57 1.370 2.193 0.000 10.000 DAS 28-ESR: Disease Activity Score-28 Erythrocyte Sedimentation Rate (ESR), DAS 28-C: Disease Activity Score-28 C Reactive Protein (CRP), CDAI: Clinical Disease Activity Index, SDAI: Simplified Disease Activity Index, TJC: Tender joint count, SJC: Swollen joint jount Table 4. Patient characteristics of the case group Patients (n), Percentage (%) Treatment Biologics 10 (17.5) Nonbiologics 40 (70.2) None 7 (12.3) Hand-wrist involvement Yes 23 (40.4) No 34 (59.6) DAS 28-ESR Remission (3.2-5.1) 17(29.8) High disease activity (>5.1) 9 (15.8) DAS 28-CRP Remission (3.2-5.1) 22 (38.6) High disease activity (>5.1) 7 (12.3) SDAI Remission (11-26) 18 (31.6) High disease activity (>26) 10 (17.5) CDAI Remission (10-22) 20 (35.1) High disease activity (>22) 8 (14) Table 4 presents the distributions of treatment type, joint involvement status and disease activity level among patients in the case group. Regarding treatment, 17.5% of patients received biologic therapy, 70.2% were on disease-modifying antirheumatic drugs (DMARDs), and 12.3% were newly diagnosed and/or not on medication. Hand and wrist involvement was present in 59.6% of patients. According to the disease activity categories, 35.1% of the DAS28-ESR patients were in remission, 19.3% had low disease activity, 29.8% had moderate disease activity, and 15.8% had high disease activity. According to the DAS28-CRP, remission was observed in 42.1% of the patients, moderate disease activity in 38.6%, low activity in 7.0%, and high activity in 12.3%. Similar rates were found when patients were grouped according to the SDAI and CDAI. These results suggest that disease activity was generally low to moderate in the case group; however, remission and moderate disease activity rates were lower when assessed by ESR-based scores. The results of the correlation analysis among all patients are shown in Table 5. Serum taurine levels were negatively correlated with the DAS 28-ESR (r = -0.271, p < 0.05). Although a negative association was also observed with DAS 28-CRP, it did not reach statistical significance (r = -0.253, p = 0.058). These findings suggest that taurine levels may be related to disease activity. Table 5. Correlation analysis of all patients Age RF CCP Disease duration TJC SJC pGlobal phGlobal ESR CRP DAS28 ESR DAS28 CRP SDAI CDAI HAQ- DI Taurine Taurine r -0.018 0.016 0.135 0.114 -0.099 -0.074 -0.085 -0.171 -0.152 -0.137 -0.271* -0.253 -0.197 -0.170 -0.132 1.000 p 0.875 0.886 0.232 0.400 0.380 0.512 0.452 0.130 0.178 0.226 0.041 0.058 0.142 0.206 0.244 0.000 Table 6. Correlation analysis of the case group Age RF CCP Disease duration TJC SJC Pglobal Phglobal ESR CRP DAS28 ESR DAS28 CRP SDAI CDAI HAQ- DI Taurine Taurine r -0.043 -0.021 0.095 0.114 -0.151 -0.119 -0.092 -0.268* -0.218 -0.173 -0.271* -0.253 -0.197 -0.170 -0.183 1.000 p 0.748 0.875 0.480 0.400 0.261 0.377 0.498 0.044 0.103 0.197 0.041 0.058 0.142 0.206 0.174 0.000 Within the case group, similar results were found (Table 6). Serum taurine was negatively correlated with the DAS28-ESR (r = -0.271, p < 0.05) and tended to be negatively correlated with the DAS28-CRP (r = -0.253, p = 0.058). Additionally, serum taurine levels were negatively correlated with physician global assessment (phGlobal) scores (r = -0.268, p = 0.044). Discussion The anti-inflammatory properties of taurine have been demonstrated in numerous in vitro and animal studies in the literature. To the best of our knowledge, this is the first study to evaluate serum taurine levels in relation to disease activity scores in patients with RA. Our study did not reveal a statistically significant difference in serum taurine levels between the patient and control groups. Several confounding factors may have contributed to this outcome, with dietary habits being a primary consideration. Taurine is a conditionally essential amino acid; although it can be synthesized endogenously, adequate dietary intake remains crucial for maintaining physiological levels. For example, Laidlaw et al. demonstrated that both plasma taurine concentrations and urinary taurine excretion are significantly lower in vegan individuals than in nonvegetarians [ 29 ]. In the present study, no dietary restrictions or standardizations were applied to the participants. Furthermore, concomitant medication use, variations in skeletal muscle mass, and differences in physical activity levels may also influence serum taurine concentrations. Stratification of the case group on the basis of disease activity indices did not reveal a statistically significant correlation between the serum taurine concentration and disease activity. This finding may be attributed to the limited number of patients within each disease activity subgroup. As previously noted, the majority of our cohort consisted of individuals with low to moderate disease activity. It is possible that more robust associations could be identified in studies involving a larger sample size, particularly those including patients with higher disease activity. In our study, a significant negative correlation was found between serum taurine levels and the DAS 28-ESR score, which is commonly used in routine rheumatology practice to assess disease activity in RA patients. Although a similar relationship was observed with the DAS 28-CRP score, it did not reach statistical significance. The observed negative correlation between taurine levels and disease activity suggested that disease activity may decrease as taurine levels increase. Notably, many in vitro studies have shown that not only taurine itself but also its haloamine derivatives—TauCl and TauBr—decrease the production of inflammatory cytokines such as IL-1, IL-6, and IL-8 and have dual effects on TNF-alpha (increasing TNF-alpha production at low concentrations and decreasing it at high concentrations) [ 18 , 21 , 28 ]. The absence of haloamine compound measurements in our study may have limited its power; nevertheless, our findings still provide valuable insight. Similarly, phGlobal was negatively correlated with serum taurine levels, indicating that clinical evaluation may reflect taurine status. Conflicting results exist in the literature regarding serum taurine levels and treatment response in RA patients. For example, Gosselt et al. reported lower baseline plasma taurine levels in MTX-insufficient responders, whereas Takashi and colleagues reported decreased taurine concentrations in responders to TNF inhibitors [ 26 , 27 ]. Our study did not demonstrate such associations. Several limitations inherent to the present study warrant consideration. The relatively small sample size, which affects not only the overall patient cohort but also the individual case subgroups and the control population, potentially limits the statistical power and generalizability of the findings. Additionally, concomitant medications used by participants for their comorbid conditions may have influenced their serum taurine levels. Moreover, the study design did not incorporate serial measurements of serum taurine during posttreatment follow-up in the case group, precluding assessment of temporal changes in taurine levels in response to therapeutic interventions. These methodological constraints should be addressed in future investigations to enhance the validity and reliability of the results. Despite these limitations, the present study highlights the potential role of taurine as a biomarker for disease activity in rheumatoid arthritis (RA), addressing a relatively novel and underexplored area within the current scientific literature. Conclusion Reliable inflammatory biomarkers for assessing RA disease activity remain limited. The most commonly used markers are ESR and CRP. In this study, we demonstrated an association between serum taurine levels and disease activity. However, further larger-scale and well-designed studies are needed before serum taurine and/or its derivatives can be recommended for routine clinical use. Moreover, the observed inverse relationship between taurine levels and RA disease activity raises the possibility that taurine supplementation could serve as an adjunctive therapeutic strategy. Future well-designed prospective studies may provide valuable insights into this potential. Abbreviations RA Rheumatoid Arthritis ACR American College of Rheumatology EULAR European League Against Rheumatism DAS 28 Disease Activity Score 28 ESR Erythrocyte Sedimentation Rate CRP C-Reactive Protein CDAI Clinical Disease Activity Index SDAI Simplified Disease Activity Index RF Rheumatoid Factor CCP Cyclic Citrullinated Peptide phGlobal Physician Global Assessment pGlobal Patient Global Assessment TJC Tender Joint Count SJC Swollen Joint Count HAQ-DI Health Assessment Questionnaire- Disability Index H₂O₂ Hydrogen Peroxide O₂⁻ Superoxide Anion NO Nitric Oxide MAPK Mitogen-Activated Protein Kinase FLS Fibroblast-Like Synoviocytes Tau-Cl Taurine Chloramine Tau-Br Taurine Bromamine IL-6 Interleukin-6 IL-8 Interleukin-8 IL-12 Interleukin-12 PGE₂ Prostaglandin E₂ IL-1β Interleukin-1 Beta TNF-α Tumor Necrosis Factor Alpha CO Carbon Monoxide MMP-1 Matrix Metalloproteinase-1 MMP-3 Matrix Metalloproteinase-3 MTX Methotrexate Declarations Ethics approval and consent to participate Informed consent was obtained from all study participants. The study was approved by the Fırat University Non-Interventional Research Ethics Committee (number 2024/11-29, dated 01.08.2024) and conducted in accordance with the Declaration of Helsinki. Consent for Publication Not Applicable Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no conflicts of interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ contributions Conceptualization: T.Ş., D.Ş.; Methodology: T.Ş., D.Ş.; Investigation: T.Ş., M.G., P.Ö.; Writing – original draft: T.Ş.; Writing – review and editing: T.Ş., D.Ş., M.G., P.Ö.; Supervision: T.Ş. TŞ takes responsibility for the overall content as the guarantor. All the authors read and approved the final manuscript. Acknowledgments We would like to thank the rheumatology and microbiology staff of Elazığ Fethi Sekin City Hospital for their support. References Santulli G, Kansakar U, Varzideh F, Mone P, Jankauskas SS, Lombardi A. Functional Role of Taurine in Aging and Cardiovascular Health: An Updated Overview. Nutrients. 2023;15(19):4236. 10.3390/nu15194236 . PMID: 37836520; PMCID: PMC10574552. Weinstein CL, Haschemeyer RH, Griffith OW. In vivo studies of cysteine metabolism. Use of D-cysteinesulfinate, a novel cysteinesulfinate decarboxylase inhibitor, to probe taurine and pyruvate synthesis. J Biol Chem. 1988;263(32):16568–79. PMID: 3182803. Drake MR, De La Rosa J, Stipanuk MH. Metabolism of cysteine in rat hepatocytes. Evidence for cysteinesulphinate-independent pathways. Biochem J. 1987;244(2):279–86. 10.1042/bj2440279 . PMID: 3117038; PMCID: PMC1147988. Sbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway. Br J Pharmacol. 2019;176(4):583–93. 10.1111/bph.14446 . Epub 2018 Aug 23. PMID: 30007014; PMCID: PMC6346075. Aerts L, Van Assche FA. Taurine and taurine-deficiency in the perinatal period. J Perinat Med . 2002;30(4):281-6. 10.1515/JPM.2002.040 . PMID: 12235714. Marcinkiewicz J, Kontny E. Taurine and inflammatory diseases. Amino Acids. 2014;46(1):7–20. 10.1007/s00726-012-1361-4 . Epub 2012 Jul 19. PMID: 22810731; PMCID: PMC3894431. Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol . 2009;87(2):91 – 9. 10.1139/Y08-110 . PMID: 19234572. Wang L, Zhao N, Zhang F, Yue W, Liang M. Effect of taurine on leucocyte function. Eur J Pharmacol. 2009;616(1–3):275–80. 10.1016/j.ejphar.2009.05.027 . Epub 2009 May 31. PMID: 19490912. Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42(6):2223–32. 10.1007/s00726-011-0962-7 . Epub 2011 Jun 21. PMID: 21691752. Jong CJ, Ito T, Mozaffari M, Azuma J, Schaffer S. Effect of beta-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content. J Biomed Sci. 2010;17(1):S25. 10.1186/1423-0127-17-S1-S25 . PMID: 20804600; PMCID: PMC2994391. Cozzi R, Ricordy R, Bartolini F, Ramadori L, Perticone P, De Salvia R. Taurine and ellagic acid: two differently acting natural antioxidants. Environ Mol Mutagen . 1995;26(3):248 – 54. 10.1002/em.2850260310 . PMID: 7588651. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J. 1988;256(1):251–5. 10.1042/bj2560251 . PMID: 2851980; PMCID: PMC1135395. Goodman CA, Horvath D, Stathis C, Mori T, Croft K, Murphy RM, et al. Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation. J Appl Physiol (1985). 2009;107(1):144–54. 10.1152/japplphysiol.00040.2009 . Epub 2009 May 7. PMID: 19423840; PMCID: PMC2711783. Parvez S, Tabassum H, Banerjee BD, Raisuddin S. Taurine prevents tamoxifen-induced mitochondrial oxidative damage in mice. Basic Clin Pharmacol Toxicol. 2008;102(4):382–7. 10.1111/j.1742-7843.2008.00208.x . Epub 2008 Feb 29. PMID: 18312495. Timbrell JA, Seabra V, Waterfield CJ. The in vivo and in vitro protective properties of taurine. Gen Pharmacol . 1995;26(3):453 – 62. 10.1016/0306-3623(94)00203-y . PMID: 7789717. Gordon RE, Heller RF, Heller RF. Taurine protection of lungs in hamster models of oxidant injury: a morphologic time study of paraquat and bleomycin treatment. Adv Exp Med Biol . 1992;315:319 – 28. 10.1007/978-1-4615-3436-5_38 . PMID: 1380761. Baliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, Spandidos DA, et al. Protective role of taurine against oxidative stress (Review). Mol Med Rep. 2021;24(2):605. 10.3892/mmr.2021.12242 . Epub 2021 Jun 29. PMID: 34184084; PMCID: PMC8240184. Kontny E, Grabowska A, Kowalczewski J, Kurowska M, Janicka I, Marcinkiewicz J et al. Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Rheum . 1999;42(12):2552-60. 10.1002/1529-0131(199912)42:123.0.CO;2-V . PMID: 10616000. Kontny E, Chorazy-Massalska M, Rudnicka W, Marcinkiewicz J, Maśliński W. Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytes. Amino Acids. 2007;32(3):447–52. 10.1007/s00726-006-0368-0 . Epub 2006 Jul 31. PMID: 16868648. Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W. Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. Arthritis Rheum . 2003;48(6):1551-5. 10.1002/art.10975 . PMID: 12794822. Chorazy M, Kontny E, Marcinkiewicz J, Maśliński W. Taurine chloramine modulates cytokine production by human peripheral blood mononuclear cells. Amino Acids . 2002;23(4):407 – 13. 10.1007/s00726-002-0204-0 . PMID: 12436208. Marcinkiewicz J, Walczewska M, Olszanecki R, Bobek M, Biedroń R, Dulak J et al. Taurine haloamines and heme oxygenase-1 cooperate in the regulation of inflammation and attenuation of oxidative stress. Adv Exp Med Biol . 2009;643:439 – 50. 10.1007/978-0-387-75681-3_46 . PMID: 19239176. Kim KS, Park EK, Ju SM, Jung HS, Bang JS, Kim C, et al. Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes. Arthritis Res Ther. 2007;9(4):R80. 10.1186/ar2279 . PMID: 17697361; PMCID: PMC2206390. Kishikawa T, Maeda Y, Nii T, Arase N, Hirata J, Suzuki K, et al. Increased levels of plasma nucleotides in patients with rheumatoid arthritis. Int Immunol. 2021;33(2):119–24. 10.1093/intimm/dxaa059 . PMID: 32866240; PMCID: PMC7846180. Kang KY, Lee SH, Jung SM, Park SH, Jung BH, Ju JH. Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid. J Rheumatol. 2015;42(11):2003–11. 10.3899/jrheum.141505 . Epub 2015 Sep 1. PMID: 26329338. Gosselt HR, Muller IB, Jansen G, van Weeghel M, Vaz FM, Hazes JMW, et al. Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheumatoid Arthritis. J Pers Med. 2020;10(4):271. 10.3390/jpm10040271 . PMID: 33321888; PMCID: PMC7768454. Takahashi S, Saegusa J, Onishi A, Morinobu A. Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients. Rheumatology (Oxford) . 2019;58(12):2153–2161. 10.1093/rheumatology/kez199 . PMID: 31143951. Chorazy-Massalska M, Kontny E, Kornatka A, Rell-Bakalarska M, Marcinkiewicz J, Maśliński W. The effect of taurine chloramine on pro-inflammatory cytokine production by peripheral blood mononuclear cells isolated from rheumatoid arthritis and osteoarthritis patients. Clin Exp Rheumatol. 2004 Nov-Dec;22(6):692–8. PMID: 15638042. Laidlaw SA, Shultz TD, Cecchino JT, Kopple JD. Plasma and urine taurine levels in vegans. Am J Clin Nutr. 1988;47(4):660-3. 10.1093/ajcn/47.4.660 . PMID: 3354491. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-6893961","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":478675922,"identity":"3fe8e5e9-cbc7-4732-a6a1-e6d619250bd3","order_by":0,"name":"Tuncer Şak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDCCAwgmM8MHIMnGTlgLYwNMC+MMkBZmUrQw80Asww/4bh9gf8y7w07OvP/wY2ObX9vk+ZgZGD98zMGtRfJcAmMz75lkY5kbacbJuX23DduYGZglZ27DrcXgDANQS9uBxBkSDMaHc3tuMwK1sDHzEqGlfgb/8c+HLXtu2xOtJUGCIcc4meHH7USCWiTPMDbOnNuWbDhDIqfYsLfhdnIbM2MzXr/wnWE+8OFtm528BP/xzRI//ty2nd/efPDDRzxaGBDRAmK3oYsQBn9IUTwKRsEoGAUjBQAAiqRNQl82T0sAAAAASUVORK5CYII=","orcid":"","institution":"Elazığ Fethi Sekin City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tuncer","middleName":"","lastName":"Şak","suffix":""},{"id":478675924,"identity":"f73e744b-f394-4eba-9fd5-0dde2a1295aa","order_by":1,"name":"Mustafa Gür","email":"","orcid":"","institution":"Fırat University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"","lastName":"Gür","suffix":""},{"id":478675925,"identity":"f72be2d7-7802-442f-a205-be90d211a27d","order_by":2,"name":"Duygu Şak","email":"","orcid":"","institution":"Elazığ Fethi Sekin City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Duygu","middleName":"","lastName":"Şak","suffix":""},{"id":478675926,"identity":"af526cff-765f-4ee4-8d5d-d6fd21655a3e","order_by":3,"name":"Pınar Öner","email":"","orcid":"","institution":"University of Health Sciences Elazığ Fethi Sekin City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pınar","middleName":"","lastName":"Öner","suffix":""}],"badges":[],"createdAt":"2025-06-14 12:38:06","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6893961/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6893961/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86134177,"identity":"f1479339-3a30-4abc-972c-44b4394ae073","added_by":"auto","created_at":"2025-07-07 07:24:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":584184,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6893961/v1/b81af1db-95e1-4bc7-86fa-27e300abd4be.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The relationship between serum taurine and disease activity indices in rheumatoid arthritis patients","fulltext":[{"header":"Background","content":"\u003cp\u003eTaurine (also known as 2-aminoethanesulfonic acid) is a sulfur-containing semiessential amino acid found in various tissues, including the brain, kidney, liver, and skeletal muscles. While it can be synthesized in the liver, kidney, and, to a lesser extent, in the brain via the cysteine sulfinate and transsulfuration pathways, dietary intake is necessary. Taurine-rich foods include meat, fish, poultry, and dairy products [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition to its role in various metabolic pathways, such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation, and membrane stabilization, the anti-inflammatory effects of taurine have also been reported in multiple studies [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe anti-inflammatory effects of taurine may occur through several mechanisms. Its antioxidant properties include modulation of mitochondrial respiratory chain subunit translation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]; detoxification of hydrogen peroxide (H₂O₂), superoxide anion (O₂⁻), hydroxyl radicals (OH), and nitric oxide (NO) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]; reduction in lipid peroxidation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]; and membrane stabilization [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additionally, the inhibition of mitogen-activated protein kinase (MAPK) activation and the suppression of proinflammatory cytokine expression play important roles in its anti-inflammatory effects [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral in vitro, animal, and limited human studies have investigated the inhibition of proinflammatory cytokine expression by taurine. Kontny et al. demonstrated, via fibroblast-like synoviocytes (FLSs) obtained from rheumatoid arthritis (RA) patients, that taurine haloamines\u0026mdash;taurine chloramine (Tau-Cl) and taurine bromamine (Tau-Br)\u0026mdash;inhibit the production of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and prostaglandin E₂ (PGE₂), as well as cell proliferation, in a dose-dependent manner [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Chorazy et al. reported that Tau-Cl inhibited the production of interleukin-1β (IL-1β) and IL-6 and, at relatively high concentrations, tumor necrosis factor alpha (TNF-α) in peripheral blood mononuclear cells stimulated with bacterial lipopolysaccharides from healthy volunteers [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Similarly, Tau-Cl, Tau-Br, and carbon monoxide (CO) were shown to inhibit TNF-α, IL-6, and interleukin-12 (IL-12) production in a dose-dependent manner, while Tau-Cl was also found to inhibit matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) via different pathways [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMetabolomic profile analyses have revealed elevated taurine levels and activation of taurine metabolic pathways in the serum and synovial fluid of RA patients [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, studies investigating treatment response prediction in RA patients have produced conflicting results. For example, Gosselt et al. reported that baseline plasma taurine levels were lower in early RA patients who did not respond to methotrexate (MTX) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In contrast, Takahashi et al. reported lower mean taurine levels in patients who responded to TNF inhibitors [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we aimed to investigate whether there is a correlation between serum taurine levels and disease characteristics, inflammatory markers, and composite activity scales in patients with RA.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA prospective single-center case‒control study was conducted between August 2024 and April 2025. All participants were selected from patients admitted to the rheumatology clinics at Elazığ Fethi Sekin City Hospital. Patients who were diagnosed with RA according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis classification criteria were included. Disease activity was assessed via the Disease Activity Score (DAS) 28-Erythrocyte Sedimentation Rate (ESR), DAS 28-C Reactive Protein (CRP), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Patients with no inflammatory rheumatic pathology detected through clinical, laboratory, and/or imaging evaluations were included in the control group.\u003c/p\u003e \u003cp\u003eAdditionally, patients\u0026rsquo; age, sex, disease duration, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels, medications, number of tender and swollen joints, hand and wrist involvement, patient and physician global assessment (pGlobal and phGlobal) scores, ESR and CRP levels, and health assessment questionnaire - disability index (HAQ-DI) scores were recorded.\u003c/p\u003e \u003cp\u003ePatients aged 18 years and older who provided informed consent were included in the study. The included patients included those diagnosed with RA, newly diagnosed RA patients, and individuals without any signs of inflammatory rheumatic disease. Patients with additional inflammatory diseases, those receiving systemic immunosuppressive and/or corticosteroid treatment for other reasons, those showing signs of infection during evaluation, and pregnant patients were excluded.\u003c/p\u003e \u003cp\u003eBlood samples were collected from both the patient and control groups after a 12-hour fasting period in tubes containing aprotinin (BD Vacutainer SST II Advance, BD, Plymouth, UK). The samples were centrifuged at 2000\u0026ndash;3000 rpm for 20 minutes, and the plasma was aliquoted into small-volume tubes for storage and analysis. All the plasma samples were stored at \u0026minus;\u0026thinsp;20\u0026deg;C until the day of the assay.\u003c/p\u003e \u003cp\u003ePlasma taurine levels were measured via a Human Taurine ELISA Kit (catalog no: SL3146Hu, SUNLONG BIOTECH, China) following the manufacturer\u0026rsquo;s instructions. The absorbance was measured with a Chromate 4300 microplate reader (Awareness Technology, Palm City, USA). The detection limit of the assay for taurine was 5 pg/mL. The intra-assay and interassay coefficients of variation for plasma taurine were \u0026lt;\u0026thinsp;10% and \u0026lt;\u0026thinsp;12%, respectively.\u003c/p\u003e \u003cp\u003eData analysis was performed via SPSS version 22.0 (Statistical Package for the Social Sciences). Descriptive statistics, including the mean, standard deviation, minimum, and maximum values, were calculated to summarize the variables\u0026rsquo; basic characteristics. Categorical variables are presented as frequencies (n) and percentages (%). Independent samples t tests were used for group comparisons when parametric assumptions were met, and chi-square tests were used for categorical variables. Pearson correlation analyses were conducted to determine relationships between variables. A significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered for all analyses. Data normality and suitability for parametric tests were assessed before analysis. The results are presented in tables with the indicated statistical significance levels.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\" width=\"584\" height=\"315\"\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 summarizes the descriptive characteristics of the study participants. In the case group, 38.6% (n=22) were male, and 61.4% (n=35) were female, whereas in the control group, 39.1% (n=9) were male, and 60.9% (n=14) were female. Overall, 38.8% of the participants were male, and 61.3% were female. There was no significant difference in sex distribution between the groups (\u0026chi;\u0026sup2; = 0.002, p = 0.580). The mean age was 50.82 years (SD = 13.81) in the case group and 48.39 years (SD = 12.15) in the control group. The age difference was not statistically significant (t = 0.737, p = 0.463). Thus, the case and control groups were comparable in terms of age and sex.\u003c/p\u003e\n\u003cp\u003eAccording to the analysis comparing the case and control groups in terms of selected biochemical and clinical parameters, no significant difference was found pGlobal and serum taurine levels (Table 2).\u003c/p\u003e\n\u003cp\u003eTable 2. Clinical and biochemical parameters of the case and control groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 20px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003eCase (n=57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 27px;\"\u003e\n \u003cp\u003eControl (n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eSd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eSs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eSs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eRF (IU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e74.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e104.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e6.260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e8.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e3.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eAnti CCP (IU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e111.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e77.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e6.842\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003epGlobal (0-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e50.530\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e27.866\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e43.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e31.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.982\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.329\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003ephGlobal (0-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e42.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e29.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e11.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e6.944\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eESR (mm/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e18.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e14.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e7.650\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e6.176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e3.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eCRP (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e14.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e23.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e4.909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e4.518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e1.882\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eHAQ-DI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e1.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.707\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e3.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eSerum taurine (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e94.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e87.916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e76.887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e42.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIndependent groups T- test\u003c/p\u003e\n\u003cp\u003eWhen the characteristics of the case group were examined, it was seen that the mean disease duration was 7.89 (Sd=9,15) years, and the patient group could be grouped as having low disease activity based on DAS 28-ESR and DAS 28-CRP while could be grouped as moderate disease activity based on other scales (Table 3).\u003c/p\u003e\n\u003cp\u003eTable 3. Patient characteristics of the case group\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"74%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eSd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eMin.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eMax.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eDisease duration (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e7.890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e9.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e38.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eDAS 28-ESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e3.313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e6.310\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eDAS 28-CRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e3.248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e6.320\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eSDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e13.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e11.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e47.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eCDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e12.528\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e9.549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e37.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eTJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2.250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e3.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e16.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eSJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2.193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e10.000\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\u003eDAS 28-ESR: Disease Activity Score-28 Erythrocyte Sedimentation Rate (ESR), DAS 28-C: Disease Activity Score-28 C Reactive Protein (CRP), CDAI: Clinical Disease Activity Index, SDAI: Simplified Disease Activity Index, \u0026nbsp;TJC: Tender joint count, \u0026nbsp;SJC: \u0026nbsp; Swollen joint jount\u003c/p\u003e\n\u003cp\u003eTable 4. Patient characteristics of the case group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003ePatients (n), Percentage (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eBiologics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eNonbiologics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e40 (70.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e7 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eHand-wrist involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e23 (40.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e34 (59.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eDAS 28-ESR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eRemission \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026lt;2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e20 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eLow disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(2.6-3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e11(19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eModerate disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;3.2-5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e17(29.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eHigh disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026gt;5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e9 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eDAS 28-CRP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eRemission \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026lt;2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e24 (42.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eLow disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(2.6-3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e4 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eModerate disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;3.2-5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e22 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eHigh disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026gt;5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e7 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eSDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eRemission \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026lt;3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e8 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eLow disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(3.3-11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e21 (36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eModerate disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;11-26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e18 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eHigh disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eCDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eRemission \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (\u0026lt;2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e9 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eLow disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(2.8-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e20 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eModerate disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;10-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e20 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eHigh disease activity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(\u0026gt;22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e8 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 presents the distributions of treatment type, joint involvement status and disease activity level among patients in the case group. Regarding treatment, 17.5% of patients received biologic therapy, 70.2% were on disease-modifying antirheumatic drugs (DMARDs), and 12.3% were newly diagnosed and/or not on medication. Hand and wrist involvement was present in 59.6% of patients.\u003c/p\u003e\n\u003cp\u003eAccording to the disease activity categories, 35.1% of the DAS28-ESR patients were in remission, 19.3% had low disease activity, 29.8% had moderate disease activity, and 15.8% had high disease activity. According to the DAS28-CRP, remission was observed in 42.1% of the patients, moderate disease activity in 38.6%, low activity in 7.0%, and high activity in 12.3%. Similar rates were found when patients were grouped according to the SDAI and CDAI.\u003c/p\u003e\n\u003cp\u003eThese results suggest that disease activity was generally low to moderate in the case group; however, remission and moderate disease activity rates were lower when assessed by ESR-based scores.\u003c/p\u003e\n\u003cp\u003eThe results of the correlation analysis among all patients are shown in Table 5. Serum taurine levels were negatively correlated with the DAS 28-ESR (r = -0.271, p \u0026lt; 0.05). Although a negative association was also observed with DAS 28-CRP, it did not reach statistical significance (r = -0.253, p = 0.058). These findings suggest that taurine levels may be related to disease activity.\u003c/p\u003e\n\u003cp\u003eTable 5. Correlation analysis of all patients\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"113%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eCCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDisease duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eTJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eSJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003epGlobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003ephGlobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDAS28 ESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDAS28 CRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eSDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eCDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eHAQ- DI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eTaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eTaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e-0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.271*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e-0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.886\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.000\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\u003eTable 6. Correlation analysis of the case group\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"113%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003eCCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDisease duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eTJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eSJC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003ePglobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003ePhglobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDAS28 ESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eDAS28 CRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eSDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eCDAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eHAQ- DI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eTaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5px;\"\u003e\n \u003cp\u003eTaurine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e-0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e-0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.268*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.271*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e-0.170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e-0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWithin the case group, similar results were found (Table 6). Serum taurine was negatively correlated with the DAS28-ESR (r = -0.271, p \u0026lt; 0.05) and tended to be negatively correlated with the DAS28-CRP (r = -0.253, p = 0.058). Additionally, serum taurine levels were negatively correlated with physician global assessment (phGlobal) scores (r = -0.268, p = 0.044).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe anti-inflammatory properties of taurine have been demonstrated in numerous in vitro and animal studies in the literature. To the best of our knowledge, this is the first study to evaluate serum taurine levels in relation to disease activity scores in patients with RA.\u003c/p\u003e \u003cp\u003eOur study did not reveal a statistically significant difference in serum taurine levels between the patient and control groups. Several confounding factors may have contributed to this outcome, with dietary habits being a primary consideration. Taurine is a conditionally essential amino acid; although it can be synthesized endogenously, adequate dietary intake remains crucial for maintaining physiological levels. For example, Laidlaw et al. demonstrated that both plasma taurine concentrations and urinary taurine excretion are significantly lower in vegan individuals than in nonvegetarians [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In the present study, no dietary restrictions or standardizations were applied to the participants. Furthermore, concomitant medication use, variations in skeletal muscle mass, and differences in physical activity levels may also influence serum taurine concentrations.\u003c/p\u003e \u003cp\u003eStratification of the case group on the basis of disease activity indices did not reveal a statistically significant correlation between the serum taurine concentration and disease activity. This finding may be attributed to the limited number of patients within each disease activity subgroup. As previously noted, the majority of our cohort consisted of individuals with low to moderate disease activity. It is possible that more robust associations could be identified in studies involving a larger sample size, particularly those including patients with higher disease activity.\u003c/p\u003e \u003cp\u003eIn our study, a significant negative correlation was found between serum taurine levels and the DAS 28-ESR score, which is commonly used in routine rheumatology practice to assess disease activity in RA patients. Although a similar relationship was observed with the DAS 28-CRP score, it did not reach statistical significance. The observed negative correlation between taurine levels and disease activity suggested that disease activity may decrease as taurine levels increase.\u003c/p\u003e \u003cp\u003eNotably, many in vitro studies have shown that not only taurine itself but also its haloamine derivatives\u0026mdash;TauCl and TauBr\u0026mdash;decrease the production of inflammatory cytokines such as IL-1, IL-6, and IL-8 and have dual effects on TNF-alpha (increasing TNF-alpha production at low concentrations and decreasing it at high concentrations) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The absence of haloamine compound measurements in our study may have limited its power; nevertheless, our findings still provide valuable insight.\u003c/p\u003e \u003cp\u003eSimilarly, phGlobal was negatively correlated with serum taurine levels, indicating that clinical evaluation may reflect taurine status.\u003c/p\u003e \u003cp\u003eConflicting results exist in the literature regarding serum taurine levels and treatment response in RA patients. For example, Gosselt et al. reported lower baseline plasma taurine levels in MTX-insufficient responders, whereas Takashi and colleagues reported decreased taurine concentrations in responders to TNF inhibitors [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Our study did not demonstrate such associations.\u003c/p\u003e\u003cp\u003eSeveral limitations inherent to the present study warrant consideration. The relatively small sample size, which affects not only the overall patient cohort but also the individual case subgroups and the control population, potentially limits the statistical power and generalizability of the findings. Additionally, concomitant medications used by participants for their comorbid conditions may have influenced their serum taurine levels. Moreover, the study design did not incorporate serial measurements of serum taurine during posttreatment follow-up in the case group, precluding assessment of temporal changes in taurine levels in response to therapeutic interventions. These methodological constraints should be addressed in future investigations to enhance the validity and reliability of the results.\u003c/p\u003e \u003cp\u003eDespite these limitations, the present study highlights the potential role of taurine as a biomarker for disease activity in rheumatoid arthritis (RA), addressing a relatively novel and underexplored area within the current scientific literature.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eReliable inflammatory biomarkers for assessing RA disease activity remain limited. The most commonly used markers are ESR and CRP. In this study, we demonstrated an association between serum taurine levels and disease activity. However, further larger-scale and well-designed studies are needed before serum taurine and/or its derivatives can be recommended for routine clinical use.\u003c/p\u003e \u003cp\u003eMoreover, the observed inverse relationship between taurine levels and RA disease activity raises the possibility that taurine supplementation could serve as an adjunctive therapeutic strategy. Future well-designed prospective studies may provide valuable insights into this potential.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRheumatoid Arthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican College of Rheumatology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEULAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean League Against Rheumatism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDAS 28\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisease Activity Score 28\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eErythrocyte Sedimentation Rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-Reactive Protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDAI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eClinical Disease Activity Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDAI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSimplified Disease Activity Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRheumatoid Factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCyclic Citrullinated Peptide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ephGlobal\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePhysician Global Assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003epGlobal\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatient Global Assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTJC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTender Joint Count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSJC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSwollen Joint Count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHAQ-DI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHealth Assessment Questionnaire- Disability Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH₂O₂\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHydrogen Peroxide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eO₂⁻\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuperoxide Anion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNitric Oxide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMAPK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMitogen-Activated Protein Kinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFibroblast-Like Synoviocytes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTau-Cl\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTaurine Chloramine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTau-Br\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTaurine Bromamine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-6\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-8\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-8\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-12\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-12\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePGE₂\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstaglandin E₂\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-1β\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-1 Beta\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNF-α\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor Necrosis Factor Alpha\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCarbon Monoxide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMMP-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMatrix Metalloproteinase-1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMMP-3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMatrix Metalloproteinase-3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMTX\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all study participants. The study was approved by the Fırat University Non-Interventional Research Ethics Committee (number 2024/11-29, dated 01.08.2024) and conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: T.Ş., D.Ş.; Methodology: T.Ş., D.Ş.; Investigation: T.Ş., M.G., P.\u0026Ouml;.; Writing \u0026ndash; original draft: T.Ş.; Writing \u0026ndash; review and editing: T.Ş., D.Ş., M.G., P.\u0026Ouml;.; Supervision: T.Ş. TŞ takes responsibility for the overall content as the guarantor. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the rheumatology and microbiology staff of Elazığ Fethi Sekin City Hospital for their support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSantulli G, Kansakar U, Varzideh F, Mone P, Jankauskas SS, Lombardi A. Functional Role of Taurine in Aging and Cardiovascular Health: An Updated Overview. Nutrients. 2023;15(19):4236. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu15194236\u003c/span\u003e\u003cspan address=\"10.3390/nu15194236\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 37836520; PMCID: PMC10574552.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeinstein CL, Haschemeyer RH, Griffith OW. In vivo studies of cysteine metabolism. Use of D-cysteinesulfinate, a novel cysteinesulfinate decarboxylase inhibitor, to probe taurine and pyruvate synthesis. J Biol Chem. 1988;263(32):16568\u0026ndash;79. PMID: 3182803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrake MR, De La Rosa J, Stipanuk MH. Metabolism of cysteine in rat hepatocytes. Evidence for cysteinesulphinate-independent pathways. Biochem J. 1987;244(2):279\u0026ndash;86. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1042/bj2440279\u003c/span\u003e\u003cspan address=\"10.1042/bj2440279\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 3117038; PMCID: PMC1147988.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway. Br J Pharmacol. 2019;176(4):583\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/bph.14446\u003c/span\u003e\u003cspan address=\"10.1111/bph.14446\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2018 Aug 23. PMID: 30007014; PMCID: PMC6346075.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAerts L, Van Assche FA. Taurine and taurine-deficiency in the perinatal period. \u003cem\u003eJ Perinat Med\u003c/em\u003e. 2002;30(4):281-6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1515/JPM.2002.040\u003c/span\u003e\u003cspan address=\"10.1515/JPM.2002.040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12235714.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcinkiewicz J, Kontny E. Taurine and inflammatory diseases. Amino Acids. 2014;46(1):7\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00726-012-1361-4\u003c/span\u003e\u003cspan address=\"10.1007/s00726-012-1361-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2012 Jul 19. PMID: 22810731; PMCID: PMC3894431.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. \u003cem\u003eCan J Physiol Pharmacol\u003c/em\u003e. 2009;87(2):91\u0026thinsp;\u0026ndash;\u0026thinsp;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1139/Y08-110\u003c/span\u003e\u003cspan address=\"10.1139/Y08-110\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 19234572.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang L, Zhao N, Zhang F, Yue W, Liang M. Effect of taurine on leucocyte function. Eur J Pharmacol. 2009;616(1\u0026ndash;3):275\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejphar.2009.05.027\u003c/span\u003e\u003cspan address=\"10.1016/j.ejphar.2009.05.027\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2009 May 31. PMID: 19490912.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42(6):2223\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00726-011-0962-7\u003c/span\u003e\u003cspan address=\"10.1007/s00726-011-0962-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2011 Jun 21. PMID: 21691752.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJong CJ, Ito T, Mozaffari M, Azuma J, Schaffer S. Effect of beta-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content. J Biomed Sci. 2010;17(1):S25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1423-0127-17-S1-S25\u003c/span\u003e\u003cspan address=\"10.1186/1423-0127-17-S1-S25\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 20804600; PMCID: PMC2994391.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCozzi R, Ricordy R, Bartolini F, Ramadori L, Perticone P, De Salvia R. Taurine and ellagic acid: two differently acting natural antioxidants. \u003cem\u003eEnviron Mol Mutagen\u003c/em\u003e. 1995;26(3):248\u0026thinsp;\u0026ndash;\u0026thinsp;54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/em.2850260310\u003c/span\u003e\u003cspan address=\"10.1002/em.2850260310\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 7588651.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J. 1988;256(1):251\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1042/bj2560251\u003c/span\u003e\u003cspan address=\"10.1042/bj2560251\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 2851980; PMCID: PMC1135395.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoodman CA, Horvath D, Stathis C, Mori T, Croft K, Murphy RM, et al. Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation. J Appl Physiol (1985). 2009;107(1):144\u0026ndash;54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1152/japplphysiol.00040.2009\u003c/span\u003e\u003cspan address=\"10.1152/japplphysiol.00040.2009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2009 May 7. PMID: 19423840; PMCID: PMC2711783.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParvez S, Tabassum H, Banerjee BD, Raisuddin S. Taurine prevents tamoxifen-induced mitochondrial oxidative damage in mice. Basic Clin Pharmacol Toxicol. 2008;102(4):382\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1742-7843.2008.00208.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1742-7843.2008.00208.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2008 Feb 29. PMID: 18312495.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTimbrell JA, Seabra V, Waterfield CJ. The in vivo and in vitro protective properties of taurine. \u003cem\u003eGen Pharmacol\u003c/em\u003e. 1995;26(3):453\u0026thinsp;\u0026ndash;\u0026thinsp;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0306-3623(94)00203-y\u003c/span\u003e\u003cspan address=\"10.1016/0306-3623(94)00203-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 7789717.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGordon RE, Heller RF, Heller RF. Taurine protection of lungs in hamster models of oxidant injury: a morphologic time study of paraquat and bleomycin treatment. \u003cem\u003eAdv Exp Med Biol\u003c/em\u003e. 1992;315:319\u0026thinsp;\u0026ndash;\u0026thinsp;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-1-4615-3436-5_38\u003c/span\u003e\u003cspan address=\"10.1007/978-1-4615-3436-5_38\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 1380761.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, Spandidos DA, et al. Protective role of taurine against oxidative stress (Review). Mol Med Rep. 2021;24(2):605. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/mmr.2021.12242\u003c/span\u003e\u003cspan address=\"10.3892/mmr.2021.12242\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Jun 29. PMID: 34184084; PMCID: PMC8240184.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKontny E, Grabowska A, Kowalczewski J, Kurowska M, Janicka I, Marcinkiewicz J et al. Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes. \u003cem\u003eArthritis Rheum\u003c/em\u003e. 1999;42(12):2552-60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/1529-0131(199912)42:12\u0026lt;2552::AID-ANR7\u0026gt;3.0.CO;2-V\u003c/span\u003e\u003cspan address=\"10.1002/1529-0131(199912)42:12%3C2552::AID-ANR7%3E3.0.CO;2-V\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 10616000.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKontny E, Chorazy-Massalska M, Rudnicka W, Marcinkiewicz J, Maśliński W. Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytes. Amino Acids. 2007;32(3):447\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00726-006-0368-0\u003c/span\u003e\u003cspan address=\"10.1007/s00726-006-0368-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2006 Jul 31. PMID: 16868648.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W. Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. \u003cem\u003eArthritis Rheum\u003c/em\u003e. 2003;48(6):1551-5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/art.10975\u003c/span\u003e\u003cspan address=\"10.1002/art.10975\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12794822.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChorazy M, Kontny E, Marcinkiewicz J, Maśliński W. Taurine chloramine modulates cytokine production by human peripheral blood mononuclear cells. \u003cem\u003eAmino Acids\u003c/em\u003e. 2002;23(4):407\u0026thinsp;\u0026ndash;\u0026thinsp;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00726-002-0204-0\u003c/span\u003e\u003cspan address=\"10.1007/s00726-002-0204-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12436208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcinkiewicz J, Walczewska M, Olszanecki R, Bobek M, Biedroń R, Dulak J et al. Taurine haloamines and heme oxygenase-1 cooperate in the regulation of inflammation and attenuation of oxidative stress. \u003cem\u003eAdv Exp Med Biol\u003c/em\u003e. 2009;643:439\u0026thinsp;\u0026ndash;\u0026thinsp;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-0-387-75681-3_46\u003c/span\u003e\u003cspan address=\"10.1007/978-0-387-75681-3_46\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 19239176.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim KS, Park EK, Ju SM, Jung HS, Bang JS, Kim C, et al. Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes. Arthritis Res Ther. 2007;9(4):R80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/ar2279\u003c/span\u003e\u003cspan address=\"10.1186/ar2279\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 17697361; PMCID: PMC2206390.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKishikawa T, Maeda Y, Nii T, Arase N, Hirata J, Suzuki K, et al. Increased levels of plasma nucleotides in patients with rheumatoid arthritis. Int Immunol. 2021;33(2):119\u0026ndash;24. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/intimm/dxaa059\u003c/span\u003e\u003cspan address=\"10.1093/intimm/dxaa059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 32866240; PMCID: PMC7846180.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang KY, Lee SH, Jung SM, Park SH, Jung BH, Ju JH. Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid. J Rheumatol. 2015;42(11):2003\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3899/jrheum.141505\u003c/span\u003e\u003cspan address=\"10.3899/jrheum.141505\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2015 Sep 1. PMID: 26329338.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGosselt HR, Muller IB, Jansen G, van Weeghel M, Vaz FM, Hazes JMW, et al. Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheumatoid Arthritis. J Pers Med. 2020;10(4):271. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jpm10040271\u003c/span\u003e\u003cspan address=\"10.3390/jpm10040271\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 33321888; PMCID: PMC7768454.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakahashi S, Saegusa J, Onishi A, Morinobu A. Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients. \u003cem\u003eRheumatology (Oxford)\u003c/em\u003e. 2019;58(12):2153\u0026ndash;2161. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rheumatology/kez199\u003c/span\u003e\u003cspan address=\"10.1093/rheumatology/kez199\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31143951.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChorazy-Massalska M, Kontny E, Kornatka A, Rell-Bakalarska M, Marcinkiewicz J, Maśliński W. The effect of taurine chloramine on pro-inflammatory cytokine production by peripheral blood mononuclear cells isolated from rheumatoid arthritis and osteoarthritis patients. Clin Exp Rheumatol. 2004 Nov-Dec;22(6):692\u0026ndash;8. PMID: 15638042.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaidlaw SA, Shultz TD, Cecchino JT, Kopple JD. Plasma and urine taurine levels in vegans. Am J Clin Nutr. 1988;47(4):660-3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ajcn/47.4.660\u003c/span\u003e\u003cspan address=\"10.1093/ajcn/47.4.660\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 3354491.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Rheumatoid arthritis, taurine, rheumatoid arthritis biomarker, taurine supplementation","lastPublishedDoi":"10.21203/rs.3.rs-6893961/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6893961/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe anti-inflammatory properties of taurine have been described in the literature. This study aims to investigate the relationship between serum taurine levels, inflammatory markers, and composite disease activity indices in patients with rheumatoid arthritis (RA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA prospective single-center case‒control study was conducted between August 2024 and April 2025 at Elazığ Fethi Sekin City Hospital. Patients diagnosed with RA on the basis of the 2010 ACR/EULAR criteria and varying disease activity levels (according to the DAS28-ESR, DAS28-CRP, CDAI, and SDAI) were enrolled. The control group consisted of individuals without inflammatory rheumatic diseases confirmed by clinical, laboratory, and/or imaging evaluation. Serum taurine levels were measured from blood samples obtained after clinical assessment and analyzed alongside inflammatory markers and disease activity scores.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFifty-seven RA patients and 23 noninflammatory controls were included. Compared with controls, RA patients had significantly greater ESR, CRP, phGlobal, and HAQ-DI scores (all p \u0026lt; 0.01). However, the serum taurine levels did not differ significantly between the groups (94.55 pg/ml vs. 76.89 pg/ml, p = 0.361). In all the participants, taurine levels were negatively correlated with the DAS28-ESR (r = -0.271, p = 0.041). Among RA patients, taurine was negatively correlated with phGlobal (r = -0.268, p = 0.044) and the DAS28-ESR. A negative correlation with DAS28-CRP was observed but did not reach statistical significance (r = -0.253, p = 0.058).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLow serum taurine levels may be associated with increased RA disease activity, particularly as assessed by the DAS28-ESR. These findings suggest a potential role for taurine in RA pathophysiology and highlight the need for larger-scale studies to explore its therapeutic implications.\u003c/p\u003e\n\u003cp\u003eClinical trial number: Not applicaple.\u003c/p\u003e","manuscriptTitle":"The relationship between serum taurine and disease activity indices in rheumatoid arthritis patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 08:25:01","doi":"10.21203/rs.3.rs-6893961/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c9a0c81-ba8f-454f-b9bd-30242dc409b4","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T07:23:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-01 08:25:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6893961","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6893961","identity":"rs-6893961","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}