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BackgroundArthritis is one of the most common causes of people's disability in the world. Recent years investigations were done to find biomarkers which can help in differentiating the type of arthritis, to evaluate the correlation between marker and disease severity. A purine nucleoside adenosine possesses anti-inflammatory activity via decreasing the level of pro-inflammatory cytokines, increasing the level of anti-inflammatory cytokines and represents one of the potent regulators of the inflammatory response. Adenosine deaminase (ADA) metabolizes adenosine to inosine, decreasing its anti-inflammatory activity. The significant elevation of ADA activity in rheumatoid arthritis (RA) and other inflammatory joint disorders has been observed. In our earlier study we have shown that the ADA activity can be used as a biomarker suitable for RA and osteoarthritis differentiation (1). The cutoff value of the enzyme activity in synovial fluid (SF) for differentiating these diseases in Armenian population has been evaluated. We observed the increasing of small-molecular (SADA, catalytic unit) to large-molecular (LADA, a complex of the catalytic unit with ADA-binding protein) isoforms ratio in RA SFs at increasing of the total activity of enzyme. The linear correlation between the initial activity and the SM/LM ratio of ADA isoforms has been shown (correlation coefficient r =0.97, P=0.0017).ObjectivesThe aim of the present investigation was to analyze the levels of ADA activity in SFs of patients with different arthritis and their probable correlation with the SADA/LADA ratios in various cases.MethodsThe SFs of RA, reactive arthritis, ankylosing spondylitis and gout patients were studied. The activity of ADA was assayed, evaluating the amount of ammonia, liberated in the reaction of adenosine deamination. To compare the levels of SADA and LADA isoforms, the SFs were subjected to gel-filtration on the column with G-200 Sephadex. The elution diagrams regarding the ADA activity in the obtained fractions were constructed.ResultsThe values of ADA activity in SFs of different arthritis mainly scatter in the higher region of the enzyme activities in SFs of RA. The elution diagrams after G-200 Sephadex gel-filtration of SFs of various arthritis manifested the absence or very low levels of SADA isoform even at high total initial activity of the enzyme. That excluded any correlation between the total activities of the enzyme and the ratios of its isoforms.ConclusionsThe earlier observed and proved in this study significant correlation between total activity of ADA and its isoforms ratio at RA might be in account of the SADA release from the damaged synoviocytes. This phenomenon appeared specific for RA and was not observed in the other arthritis types. We can conclude that the mechanism of joint inflammation at RA has some peculiarities, which may be a subject of special future study.ReferencesA.A. Antonyan et al. Adenosine deaminase activity in synovial fluid at arthritis. Proceedings of the YSU, Chemistry and biology, 2013, N3, p. 2...

mentioned five arthritis types. The activities and citrullination state of ADA isoforms were studied using appropriate colorimetric assays. RESULTS: This work revealed accumulation of SADA in RA SFs and of LADA in the SFs of four other arthritis types. The average protein citrullination, measured as A530/A280 ratio, was of 0.07 ± 0.04 (n = 5) in SADA purified from RA SFs with the initial ADA activity between 35-60 U/L. In SADA samples from RA SFs with the initial ADA activity of 70-190 U/L, the average value of protein citrullination was higher by an order (0.83 ± 0.28, n = 8). The citrullination of LADA was not registered in any of all five studied arthritis types. CONCLUSION: In SFs of RA, the citrullinated SADA is accumulated. In four other studied arthritis types, LADA is accumulated. One can suggest: in RA the citrullination of SADA prevents its binding to dipeptidyl peptidase IV and transformation to LADA. The obtained data permit the assumption of being SADA as a new citrulline containing auto-antigen applicable in RA diagnosis.

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