ADENOSINE DEAMINASE ACTIVITY IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Abstract

Although the pathogenesis of ankylosing spondylitis (AS), which is a systemic disease characterized by inflammation, is largely unknown, pro-inflammatory mediators, oxidative stress, and immunity are thought to be involved in the development and the prognosis of the disease. It was aimed in this study to reveal activities of adenosine deaminase (ADA), a cornerstone enzyme in different pathways. Twenty nine AS patients and 16 healthy volunteers were included in the study. Patients were divided into two groups as active and inactive phases. Additionally, the patients were re-grouped according to axial/peripheral involvement. ADA and myeloperoxidase (MPO) activities, and advanced oxidation protein products (AOPP) levels were measured in plasma of the study groups. While the significant increases were observed in AOPP and MPO levels in AS patients compared to the control group, when the patients were divided into subgroups, only ADA was significantly decreased in active patients. On the other hand, there was no significant difference in AOPP, MPO, and ADA levels in groups created according to axial/peripheral involvement. Based on these findings, it is thought that the decrease in ADA levels in AS patients can give an idea about the prognosis of the disease and can be used as an activity marker. Keywords: Adenosine deaminase, advanced oxidation protein products, ankylosing spondylitis, autoinflammation, myeloperoxidase.

Keywords

• Adenosine Deaminase
• Advanced Oxidation Protein Products
• Ankylosing Spondilitis
• Autoinflammation
• Myeloperoxidase

ANKİLOZAN SPONDİLİT HASTALARINDA ADENOZİN DEAMİNAZ AKTİVİTESİ

Abstract

Enflamasyon ile karakterize sistemik bir hastalık olan ankilozan spondilit (AS)’in patogenezi büyük ölçüde bilinmemekle birlikte proenflamatuvar mediyatörler, oksidatif stres ve immünitenin hastalığın gelişiminde ve prognozunda rol oynadığı düşünülmektedir. Bu çalışmada AS hastalarında, farklı yolaklarda köşe taşı bir enzim olan adenozin deaminaz (ADA)’ın aktivitesinin gösterilmesi amaçlanmıştır. Çalışmaya 29 AS hastası ve 16 sağlıklı gönüllü dâhil edildi. Hastalar aktif ve inaktif faz olarak iki gruba ayrıldı. Ek olarak hastalar aksiyel/periferik tutuluma göre yeniden gruplandırıldı. Çalışma gruplarının plazmalarında ADA ve miyeloperoksidaz (MPO) aktiviteleri ve ileri oksidasyon protein ürünleri (Advanced Oxidation Protein Products; AOPP) seviyeleri ölçüldü. AS hastalarında AOPP ve MPO düzeylerinde kontrol grubuna göre anlamlı artışlar görülürken, hastalar alt gruplara ayrıldığında sadece aktif hasta grubunda ADA aktivitesinde anlamlı azalma görüldü. Diğer taraftan, aksiyel/periferal tutuluma göre oluşturulan gruplarda AOPP, MPO ve ADA düzeylerinde anlamlı farklılık yoktu. Bu bulgulara dayanarak, AS hastalarında ADA düzeylerindeki düşüşün hastalığın prognozu hakkında fikir verebileceği ve aktivite belirteci olarak kullanılabileceği düşünülebilir.

Keywords

• Adenozin Deaminaz
• Ankilozan Spondilit
• İleri Oksidasyon Protein Ürünleri
• Miyeloperoksidaz
• Otoenflamasyon

References

1. Elalouf O, Elkayam O. Long-term safety and efficacy of infliximab for the treatment of ankylosing spondylitis. Ther Clin Risk Manag 2015; 11:1719-1726.
2. Pishgahi A, Abolhasan R, Danaii S, et al. Immunological and oxidative stress biomarkers in Ankylosing Spondylitis patients with or without metabolic syndrome. Cytokine 2020; 128:155002.
3. Tutuncu ZN, Bilgie A, Kennedy LG, Calin A. Interleukin-6, acute phase reactants and clinical status in ankylosing spondylitis. Ann Rheum Dis 1994; 53:425-426.
4. Garcia-Montoya L, Gul H, Emery P. Recent advances in ankylosing spondylitis: understanding the disease and management. F1000Res 2018; 7: 1512.
5. Gao ZW, Wang X, Zhang HZ, et al. The roles of adenosine deaminase in autoimmune diseases. Autoimmun Rev 2021; 20:102709.
6. Cronstein BN, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 2017; 13:41-51.
7. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007; 81:1-5.
8. Zhao-wei G, Zhao G, Li R, et al. Activities of serum adenosine deaminase and its isoenzymes in patients with systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis and myasthenia gravis. Akt Rheumatologie 2020; 45:348-355.

9. de Andrade KR, de Castro GR, Vicente G, et al. Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis. Int Immunopharmacol 2014; 2:481-486.
10. Barrows IR, Ramezani A, Raj DS. Inflammation, Immunity, and Oxidative Stress in Hypertension-Partners in Crime? Adv Chronic Kidney Dis 2019; 26:122-130.
11. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27:361-368.
12. Price DD, McGrath PA, Rafii A. Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 1983; 17:45-56.
13. Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath ankylosing spondylitis functional index. J Rheumatol 1994; 21:2281-2285.
14. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: The Bath ankylosing spondylitis disease activitiy index. J Rheumatol 1994; 21:2286-2291.
15. Kwan YH, Tan JJ, Phang JK, et al. Validity and reliability of the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with axial spondyloarthritis (axSpA) in Singapore. Int J Rheum Dis 2019; 22:2206-2212.
16. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206-269.
17. Witko-Sarsat V, Friedlander M, Nguyen Khoa T, et al. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 1998; 161:2524-2532.
18. Giusti G, Galanti B. Colorimetric method. In: Bergmeyer HU, editor. Methods of enzymatic analysis. Weinheim: Verlag Chemie 1984; 315-323.
19. Singh Patidar B, Meena A, Kumar M, et al. Adenosine metabolism in COPD: A study on adenosine levels, 5'-nucleotidase, adenosine deaminase and its isoenzymes activity in serum, lymphocytes and erythrocytes. COPD 2018; 15:559-571.
20. Valadbeigi S, Saghiri R, Ebrahimi-Rad M, Khatami S, Akhbari H. Adenosine deaminase activity and HLA-DRB as diagnostic markers for rheumatoid arthritis. Curr Rheumatol Rev 2019; 15:44-49.
21. Vinapamula KS, Pemmaraju SV, Bhattaram SK, Bitla AR, Manohar SM. Serum adenosine deaminase as inflammatory marker in rheumatoid arthritis. J Clin Diagn Res 2015; 9:BC08-10.
22. Antonioli L, Colucci R, La Motta C, et al. Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets 2012; 13:842-862.
23. Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 2008; 1783:673-694.
24. Zamani B, Jamali R, Jamali A. Serum adenosine deaminase may predict disease activity in rheumatoid arthritis. Rheumatol Int 2012; 32:1967-1975.
25. Zborovskiĭ AB, Mozgovaia EE, Martem'ianov VF, et al. [The clinical diagnostic value of a study of the activity of enzymes of the guanyl branch of purine metabolism in patients with ankylosing spondyloarthritis]. Ter Arkh 2010; 82:48-52.
26. Maksymowych WP. Biomarkers for diagnosis of axial spondyloarthritis, disease activity, prognosis, and prediction of response to therapy. Front Immunol 2019; 10:305.
27. Wang H, Zheng H, Ma Y. Drug treatment of ankylosing spondylitis and related complications: an overlook review. Ann Palliat Med 2020; 9:2279-2285.
28. Halliwell B: Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann Rheum Dis 1995; 54:505-510.
29. Yazici C, Köse K, Calis M, et al. Protein oxidation status in patients with ankylosing spondylitis. Rheumatology (Oxford) 2004; 43:1235-1239.
30. Feijóo M, Túnez I, Tasset I, et al. Infliximab reduces oxidative stress in ankylosing spondylitis. Clin Exp Rheumatol 2009; 27:167-168.
31. Wang L, Gao L, Jin D, et al. The relationship of bone mineral density to oxidant/antioxidant status and inflammatory and bone turnover markers in a multicenter cross-sectional study of young men with ankylosing spondylitis. Calcif Tissue Int 2015; 97:12-22.
32. Piwowar A. Advanced oxidation protein products. Part I. Mechanism of the formation, characteristics and property. Pol Merkur Lekarski 2010; 28:166-169.
33. Solmaz D, Kozacı D, Sarı İ, et al. Oxidative stress and related factors in patients with ankylosing spondylitis. Eur J Rheumatol 2016; 3:20-24.