Inflammation Parameters, Xanthine Oxidase and Anti-Xanthine Oxidase Antibodies in Synovial Fluid of Patients Suffering from Arthritis

Year 2022, , 136 - 143, 29.12.2022

Nadjet Hanachı , Lekhmici Arrar

https://doi.org/10.26650/EurJBiol.2022.1097938

Abstract

Objective: Rheumatoid arthritis (RA) is an autoimmune disease where sera and synovial fluid (SF) of suffering patients contain immune complexes formed from autoantibodies to several proteins. SF from humans with joint diseases was examined for the presence of some inflammatory parameters and autoantibodies. Materials and Methods: Antibodies in their free and complex forms were assayed by indirect ELISA. The immunoprecipitation technique was used to evaluate total IgG and IgM and complement. Results: The results showed that most RA SF was anti-ASLO negative, but they were CRP positive. Levels of complement components (C3 and C4) were highest in the group of mono-/oligo-arthritis and lowest in RA. The results showed that xanthine oxidase (XO) presence and activity were important in SF of RA patients. Moreover, free and complex anti-XO antibodies were detected in all SF with different titers throughout the groups of patients where IgG was lower than IgM. Conclusion: The studied parameters of inflammation and auto-antibodies especially against XO could serve as an evaluation of the severity of joint inflammation and in RA pathogenesis understanding.

Keywords

Autoantibodies, joint inflammation, streptolysin, Rheumatoid arthritis, xanthine oxidase, complement

References

• 1. Nilsson J, Andersson MLE, Hafström I, Svensson B, Forslind K, Ajeganova S, et al. Influence of age and sex on disease course and treatment in rheumatoid arthritis. Open Access Rheumatol: Res Reviews 2021; 13: 123-38. google scholar
• 2. Lu S, Carlsen S, Hansson AS, Holmdahl R. Immunization of rats with homologous type XI collagen leads to chronic and relapsing arthritis with different genetics and joint pathology than arthritis induced with homologous type II collagen. J Autoimmunity 2002; 18: 199-211. google scholar
• 3. Backlund J, Treschow A, Firan M, Malmstrom V, Issazadeh-Navikas S, Ward ES, et al. Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection. Eur J Immunol 2002; 32: 1773-83. google scholar
• 4. Jilani AA, Mackworth-Young CG. The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: a systematic literature review and meta-analysis. Int JRheuma-tol 2015; 2015: 728610. google scholar
• 5. Panagopoulos PK, Lambrou GI. Bone erosions in rheumatoid ar-thritis: recent developments in pathogenesis and therapeutic im-plications. J Musculoskelet Neuronal Interact 2018; 18(3): 304-19. google scholar
• 6. Rocha SdB, Baldo DC, Andrade LEC. Clinical and athophysiologic relevance of autoantibodies in rheumatoid arthritis. Adv Rheuma-tol 2019; 59:1-13. google scholar
• 7. Smith M. The Normal Synovium. Open Rheumatol J2011; 5(Suppl 1:M2): 100-6. google scholar
• 8. Chang MH, Levescot A, Nelson-Maney N, Blaustein RB, Winden KD, Morris A, et al. Arthritis flares mediated by tissue-resident memory T cells in the joint. Cell Reports 2021;37: 109902. google scholar
• 9. Polgar A, Falus A, Koo' E, Ujfalussy I, Sesztak M, Szuts I, et al. El-evated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases. Rheumatology 2003; 42:522-7. google scholar
• 10. Arrar L, Hanachi N, Rouba K, Charef N, Khennouf S, Baghiani A. An-ti-xanthine oxidase antibodies in sera and synovial fluid of patients with rheumatoid arthritis and other joint inflammations; Saudi Med J 2008; 29(6): 803-7. google scholar
• 11. Nakamura H, Masuko K, Yudoh K, Kato T, Kamada T, Kawahara T. Ef-fects of glucosamine administration on patients with rheumatoid arthritis. Rheumatol Int 2007; 27: 213-8. google scholar
• 12. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84. google scholar
• 13. Nasi S, Castelblanco M, Chobaz V, Ehirchiou D, So A, Bernabei I, Ku-sano T, et al. Xanthine oxidoreductase is involved in chondrocyte mineralization and expressed in osteoarthritic damaged cartilage. Front Cell Dev Biol 2021; 9: 612440. google scholar
• 14. Hanachi N, Charef N, Baghiani A, Khennouf S, Derradji Y, Boumer-feg S, et al. Comparison of xanthine oxidase levels in synovial fluid from patients with rheumatoid arthritis and other joint inflamma-tions. Saudi Med J 2009; 30(11): 1422-5 google scholar
• 15. Boere J, van de Lest CHA, Libregts SFWM, Arkesteijn GJA, Geerts WJC, Hoen ENMN, et al. Synovial fluid pretreatment with hyaluro-nidase facilitates isolation of CD44+ extracellular vesicles. J Extracell Vesicles 2016; 5: 1-16 google scholar
• 16. Baghiani A, Harrison R, Benboubetra M. Purification and partial characterisation of camel milk xanthine oxidoreductase. Arch Physiol Biochem 2003; 111: 407-14. google scholar
• 17. Abadeh S, Killacky J, Benboubetra M, Harrison R. Purification and partial characterization of xanthine oxidase from human milk. Bio-chim Biophys Acta 1992; 1117: 25-32. google scholar
• 18. Rousseaux-Prevost R, De Almeida M, Arrar L, Hublau P, Rousseaux J. Antibodies to sperm basic nuclear proteins detected in infertile patients by dot-immunobinding assay and by enzyme-linked im-munosorbent assay. Am J Reprod Immunol 1989; 20: 17-20. google scholar
• 19. Geerts I, De Vos N, Frans J, Mewis A. The clinical diagnostic role of antistreptolysin O antibodies. Acta Clin Belgica 2011; 66: 411-5. google scholar
• 20. Zinellu A, Mangoni AA. Serum complement C3 and C4 and COVID-19 severity and mortality: A systematic review and me-ta-analysis with meta-regression. Front Immunol 2021; 12: 96085. google scholar
• 21. Hebert LA, Cosio FG, Neff JC. Diagnostic significance of hypocom-plementemia. Kidney Int 1991; 39: 811-21. google scholar
• 22. Ng YL and Lewis WH. Circulating immune complexes of xanthine oxidase in normal subjects. Br J Biomed Sci 1994; 51: 124-7. google scholar
• 23. Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol 1983; 34: 141-212. google scholar
• 24. Mallya RK, de Beer FC, Berry H, Hamilton EDB, Mace BEW & Pepys MB. Correlation of clinical parameters of disease activity in rheu-matoid arthritis with serum concentrations of C- reactive protein and erythrocyte sedimentation rate. J Rheum 1982; 9: 224-8. google scholar
• 25. Sihvonen S, Korpela M, Mustila A and Mustonen J. The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated pep-tide antibodies, and antineutrophil cytoplasmic antibodies for mortality in patients with rheumatoid arthritis. J Rheum 2005; 32: 2089-94. google scholar
• 26. Westwood OMR, Nelson PN and Hay FC. Rheumatoid factors: What’s new? Rheum 2006; 45: 379-85. google scholar
• 27. Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: clinical applications. Disease Markers 2013; 35(6): 727-34. google scholar
• 28. Johnson DR, Kaplan EL, Sramek J, Bicova R, Havlicek J, Havlickova H et al. Laboratory diagnosis of group A streptococcal infections. Geneva (Switzerland): World Health Organization; 1996. google scholar
• 29. Massell BF. Confirmation of haemolytic streptococcus hypothesis. In: Massell BF, ed. Rheumatic Fever and Streptococcal Infection. Unravelling the mysteries of a dread disease. Boston: Harvard Uni-versity Press; 1997: p. 93-110. google scholar
• 30. Okroj M, Heinegârd D, Holmdahl R,Blom AM. Rheumatoid arthritis and the complement system. Ann Med 2007; 39(7): 517-30. google scholar
• 31. Ballanti E, Perricone C, di Muzio G, Kroegler B, Chimenti MS, Gracef-fa D, et al. Role of the complement system in rheumatoid arthritis and psoriatic arthritis: Relationship with anti-TNF inhibitors. Auto-immun Rev 2011;10: 617-23. google scholar
• 32. Blake DR, Stevens CR, Sahinoglu T, Ellis G, Gaffney K, Edmonds S et al. Xanthine oxidase; four roles for the enzyme in rheumatoid pathology. Biochem Soc Trans 1997; 25: 812-6. google scholar
• 33. Stevens CR, Benboubetra M, Harrison R, Sahinoglu T, Smith EC, Blake DR. Localization of xanthine oxidase to synovial endotheli-um. Ann Rheum Dis 1991; 199750: 760-2. google scholar
• 34. Miesel R, Zuber M. Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases. Inflammation1993; 17(5): 551-61. google scholar
• 35. Al-Muhtaseb N, Al-Kaissi E, Thawaini AJ, Eldeen ZM, Al-Muhtaseb, Al-Saleh B. The role of human xanthine oxidoreductase (HXOR), anti-HXOR antibodies, and microorganisms in synovial fluid of pa-tients with joint inflammation. Rheumatol Int 2012; 32: 2355-62. google scholar
• 36. Brouwers H, von Hegedus JH, van der Linden E, Mahdad R, Klop-penburg M, Toes R et al. Hyaluronidase treatment of synovial fluid is required for accurate detection of inflammatory cells and solu-ble mediators. Arthritis Res Ther 2022; 24(18): 1-18. google scholar