Investigation the autoantibodies, IL-17 and IL-22in rheumatoid arthritis patients
DOI:
https://doi.org/10.12923/Keywords:
rheumatoid arthritis (RA), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), IL-17, IL-22, biological treatment, disease stagesAbstract
Rheumatoid arthritis (RA) remains a prevalent and progressive autoimmune disease worldwide, associated with substantial medical, psychological, and economic burdens.
To evaluate the role of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and the proinflammatory cytokines interleukin-17 (IL-17) and interleukin-22 (IL-22) in the development of RA, and to assess their association with disease activity and response to treatment.
A case-control study was conducted involving 150 participants, including 120 patients with RA diagnosed by a specialist according to the 2010 ACR/EULAR criteria and 30 age- and sex-matched healthy controls. Serum levels of RF, ACPA, IL-17, and IL-22 were measured using enzyme-linked immunosorbent assay (ELISA).
Significantly higher serum levels of RF and ACPA were observed in patients with RA compared with the control group. Receiver operating characteristic (ROC) curve analysis identified a cut-off value of 22.95 U/mL for RF, with 97.4% sensitivity and 90% specificity, and a cut-off value of 22.45 U/mL for ACPA, with 100% sensitivity and 100% specificity. Serum levels of IL-17 and IL-22 were also significantly increased in patients with RA compared with controls. ROC analysis revealed cut-off values of 26.86 pg/mL for IL-17 and 30.16 pg/mL for IL-22, both showing high statistical significance. Stratification according to disease severity and treatment type demonstrated that IL-17 and IL-22 levels were significantly higher in patients at stage 4 and in untreated patients compared with those at earlier disease stages and those receiving chemical, biological, or combination therapies.
The present study demonstrates that RF and ACPA levels are significantly elevated in patients with RA and exhibit high diagnostic accuracy based on optimal cut-off values. In addition, IL-17 and IL-22 levels are markedly increased, particularly in patients with advanced disease and those who are untreated. These findings indicate a strong association between elevated autoantibody and cytokine levels, disease severity, and treatment response, supporting their potential utility as biomarkers in the clinical management of RA.
References
1. Misra DP. Clinical manifestations of rheumatoid arthritis, including comorbidities, complications, and long-term follow-up. Best Pract Res Clin Rheumatol. 2025;39(1):102020. doi:10.1016/j.berh.2024.102020
2. Salinas M, Blasco Á, Flores E, Minguez M, Leiva-Salinas C. Double positivity for rheumatoid factor and anti-CCP autoantibodies: improving referral from primary care of patients suspected of having rheumatoid arthritis. Prim Health Care Res Dev. 2024;25:e6. doi:10.1017/S1463423623000695
3. Hafez AE, Abdelazeem AH, Abdelhakeem MA, Darwesh AF. Clinical utility of anti-carbamylated antibody in female patients with rheumatoid arthritis: emerging predictive value compared to anti-cyclic citrullinated peptide and rheumatoid factor. Egypt Rheumatol. 2022;44(2):175–179. doi:10.1016/j.ejr.2021.11.001
4. Chen HM, Tsai YH, Hsu CY, et al. Peptide-coated bacteriorhodopsin-based photoelectric biosensor for detecting rheumatoid arthritis. Biosensors (Basel). 2023;13(10):929. doi:10.3390/bios13100929
5. Hensvold A, Horuluoglu B, Sahlström P, et al. The human bone marrow plasma cell compartment in rheumatoid arthritis: clonal relationships and anti-citrulline autoantibody-producing cells. J Autoimmun. 2023;136:103022. doi:10.1016/j.jaut.2023.103022
6. Faihan WA, Darweesh MF. Investigating the role of miRNA-146a and IL-17 levels in progressive rheumatoid arthritis. Egypt J Immunol. 2024;31(3):71–80. doi:10.55133/eji.310308
7. Darweesh MF. Molecular characterization of ESBL genes in Citrobacter spp. and antibacterial activity of omega-3 against resistant isolates. Curr Issues Pharm Med Sci. 2017;30(3):156–161. doi:10.1515/cipms-2017-0029
8. Almurshedi SM, Alasady RA. The role of interleukin-22 in the diagnosis and evaluation of disease activity in rheumatoid arthritis. Kufa Med J. 2023;19(1):112–122. doi:10.36330/kmj.v19i1
9. Hassan LA, Majeed AA, Darweesh MF. The role of IL-12 in the etiology of SLE and its connection to HBV infection in Iraqi patients. J Commun Dis. 2022;54(1):41–46. doi:10.24321/0019.5138.202248
10. Abd El-Ghany NS, Siam IM, Monir AM. Gender impact on rheumatoid arthritis disease characteristics in a cohort of Egyptian patients. Med J Cairo Univ. 2019;87(3):1895–1899.
11. Nilsson J, Andersson MLE, Hafström I, et al. Influence of age and sex on disease course and treatment in rheumatoid arthritis. Open Access Rheumatol. 2021;13:123–138. doi:10.2147/OARRR.S306378
12. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. doi:10.1038/nrdp.2018.1
13. van Boheemen L, van Schaardenburg D. Predicting rheumatoid arthritis in at-risk individuals. Clin Ther. 2019;41(7):1286–1298. doi:10.1016/j.clinthera.2019.04.017
14. Al-Rubaye AF, Kadhim MJ, Hameed IH. Rheumatoid arthritis: history, stages, epidemiology, pathogenesis, diagnosis, and treatment. Int J Toxicol Pharmacol Res. 2017;9(2). doi:10.25258/ijtpr.v9i02.9052
15. Rönnelid J, Turesson C, Kastbom A. Autoantibodies in rheumatoid arthritis: laboratory and clinical perspectives. Front Immunol. 2021;12:685312. doi:10.3389/fimmu.2021.685312
16. Al-Saffar EA, Al-Saadi BQH, Awadh NI. Association of miRNA-146a gene polymorphism and selected immunological markers with the risk of rheumatoid arthritis in Iraqi patients. Bionatura. 2023;8(2). doi:10.21931/RB/CSS/2023.08.02.62
17. Volkov M, van Schie KA, van der Woude D. Autoantibodies and B cells: the ABC of rheumatoid arthritis pathophysiology. Immunol Rev. 2020;294(1):148–163. doi:10.1111/imr.12829
18. Haarhaus ML, Klareskog L. The lung as a target and as an initiator of rheumatoid arthritis-associated immunity: implications for interstitial lung disease. Rev Colomb Reumatol. 2024. doi:10.1016/j.rcreu.2023.09.006
19. Mahdi ZF, Mohammed SH, Hadi AR. Anti-SSA and anti-dsDNA autoantibodies in rheumatoid arthritis patients and their association with disease severity: a case-control study in Kerbala Province. Al-Rafidain J Med Sci. 2023;5:105–111. doi:10.54133/ajms.v5i.169
20. Catrina A, Krishnamurthy A, Rethi B. Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis. RMD Open. 2021;7(1):e001228. doi:10.1136/rmdopen-2020-001228
21. Orsini F, Crotti C, Cincinelli G, et al. Bone involvement in rheumatoid arthritis and spondyloarthritis: an updated review. Biology (Basel). 2023;12(10):1320. doi:10.3390/biology12101320
22. Wang J, He L, Li W, Lv S. Role of IL-17 in rheumatoid arthritis patients complicated with atherosclerosis. Front Pharmacol. 2022;13:828933. doi:10.3389/fphar.2022.828933
23. Faihan WA, Darweesh MF. Impact of serum IL-6 levels on tonsillitis and tonsillectomy patients infected with Streptococcus pyogenes. J Phys Conf Ser. 2020;1660(1):012019. doi:10.1088/1742-6596/1660/1/012019
24. Albarzinji N, Albustany D. Association of 25-hydroxyvitamin D with IL-17 inflammatory cytokines and osteoporosis in patients with rheumatoid arthritis in Kurdistan Region, Iraq. Open Rheumatol J. 2022;16:1–8. doi:10.2174/18743129-v16-e2210060
25. Li X, Lei Y, Gao Z, et al. Effect of IL-34 on T helper 17 cell proliferation and IL-17 secretion by peripheral blood mononuclear cells from patients with rheumatoid arthritis. Sci Rep. 2020;10(1):19370. doi:10.1038/s41598-020-79312-z
26. Robert M, Miossec P. IL-17 in rheumatoid arthritis and precision medicine: from synovitis expression to circulating bioactive levels. Front Med (Lausanne). 2019;6:364. doi:10.3389/fmed.2018.00364
27. Farag MA, El Debaky FE, Abd El-Rahman SM, Abd El-Khalek SM, Fawzy RM. Serum and synovial fluid interleukin-17 concentrations in rheumatoid arthritis patients: relation to disease activity, radiographic severity, and power Doppler ultrasound. Egypt Rheumatol. 2020;42(3):171–175. doi:10.1016/j.ejr.2020.02.009
28. Al-Saadany HM, Hussein MS, Gaber RA, Zaytoun HA. Th17 cells and serum IL-17 in rheumatoid arthritis patients: correlation with disease activity and severity. Egypt Rheumatol. 2016;38(1):1–7. doi:10.1016/j.ejr.2015.01.001
29. Abaas BM, Darweesh MF. Immunopathological role of miR-326, viral infection, and IL-17 concentration in patients with multiple sclerosis. Fam Med Prim Care Rev. 2024;26(3):285–290. doi:10.5114/fmpcr.2024.142005
30. Siddiqui A, Totonchian A, Ali JBJ, et al. Risk factors associated with non-responsiveness to methotrexate in patients with rheumatoid arthritis. Cureus. 2021;13(9):e18112. doi:10.7759/cureus.18112
31. Bluett J, Sergeant JC, MacGregor AJ, et al. Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study. Arthritis Res Ther. 2018;20(1):71. doi:10.1186/s13075-018-1544-9
32. Al-Ani N, Gorial F, Yasiry D, et al. Clinical outcomes in Iraqi patients with rheumatoid arthritis following earlier or later treatment with etanercept. Open Access Rheumatol. 2021;13:57–62. doi:10.2147/OARRR.S300838
33. Lopez-Pedrera C, Barbarroja N, Patiño-Trives AM, et al. Effects of biological therapies on molecular features of rheumatoid arthritis. Int J Mol Sci. 2020;21(23):9067. doi:10.3390/ijms21239067
34. Friedman B, Cronstein B. Methotrexate mechanism in the treatment of rheumatoid arthritis. Joint Bone Spine. 2019;86(3):301–307. doi:10.1016/j.jbspin.2018.07.004
35. Nile RSH, Darweesh MF, Al-Rufaie MM. Liposomal lipopolysaccharide vaccine extracted from Proteus mirabilis induces moderate TLR4 and CD14 production. Curr Issues Pharm Med Sci. 2019;32(2):81–86. doi:10.2478/cipms-2019-0016
36. Mutlu MY, Tascilar K, Schett G. Rationale, current state, and opportunities in combining biologic disease-modifying antirheumatic drugs in rheumatoid and psoriatic arthritis. Joint Bone Spine. 2023;90(5):105578. doi:10.1016/j.jbspin.2023.105578
37. Fakher YS, Shaheed OM. Interleukin-22 as a biomarker for rheumatoid arthritis in the Iraqi population. J Pharm Negat Results. 2022;13(2):209–212. doi:10.47750/pnr.2022.13.s02.29
38. Aldhaher ZA, Al-Ghurabi BH, Alwan BH. Serum levels of IL-22 and ACPA in patients with rheumatoid arthritis. J Pure Appl Microbiol. 2018;12(2):687–691. doi:10.22207/JPAM.12.2.27
39. Yap HY, Tee SZY, Wong MMT, Chow SK, Peh SC, Teow SY. Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development. Cells. 2018;7(10):161. doi:10.3390/cells7100161
40. Xuan X, Zhang L, Tian C, et al. Interleukin-22 and connective tissue diseases: emerging roles in pathogenesis and therapy. Cell Biosci. 2021;11:2. doi:10.1186/s13578-020-00504-9
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Wijdan Abdulameer Faihan, Mayada F. Darweesh (Autor)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
