AB0187 The association between activity of purine and pyrimidine metabolism enzymes and disease activity in systemic scleroderma patients
Authors: E. Mozgovaya, S. Bedina, A. Trofimenko, I. Zborovskaya
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recent studies report various metabolic disturbances in systemic scleroderma (SSc) patients. Purine and pyrimidine metabolic pathways are closely interrelated, underlying the central processes of cellular life. Alterations of the enzymes that control these metabolic conversions can disturb proliferation and differentiation of lymphocytes, therefore contributing initiation and progression of the immunopathological phenomena. <h3>Objectives</h3> to characterise enzymatic patterns of the major purine and pyrimidine metabolic pathways enzymes in blood plasma and lysed lymphocytes depending on the SSc activity. <h3>Methods</h3> 51 SSc patients and 30 healthy controls were enrolled in the study. Mean age of patients (Mean ±SD) was 42,8±1,3 years, mean SSc duration was 7,9±0,7 years. The diagnosis was verified in accordance with the international standards (ACR/.<sup>EULAR 2013</sup> Disease activity was assessed in accordance with the national classification.<sup>1</sup> Adenosine deaminase (ADA; EC 3.5.4.4); adenosine kinase (AK; EC 2.7.1.20); guanylate kinase (GK; EC 2.7.4.8), dihydroorotate dehydrogenase (DODH; EC 1.3.1.14); IMP dehydrogenase (IMPDH; EC 1.1.1.205); purine nucleoside phosphorylase (PNP; EC 2.4.2.1); thymidine kinase (TK; EC 2.7.1.21); thymidine phosphorylase (TP; EC 2.4.2.4); uracil/thymidine dehydrogenase (UDH; EC 1.17.99.4); cytidine deaminase (CDA; EC 3.5.4.5) activities were measured in blood plasma and lysed lymphocytes. <h3>Results</h3> We revealed substantial changes in enzymatic activities related to both purine and pyrimidine metabolism in SSc. The increased DODH (p&lt;0,001), IMPDH (p&lt;0,001), PNP (p&lt;0,001), TK (p&lt;0,001), TP (p&lt;0,01), UDH (p&lt;0,001) activities in plasma and AK (p&lt;0,001), IMPDH (p&lt;0,001), TK (p&lt;0,001) activities in lysed lymphocytes; the decreased ADA (p&lt;0,001), GK (p=0,02), PNP (p&lt;0,001) activities in lysed lymphocytes were observed in SSc patients in comparison with healthy controls. Plasma AK, DODH, IMPDH, PNP, TK, UDH activities positively correlated with SSc activity, as well as lymphocytic AK, IMPDH, TK activities did. Negative correlations with SSc activity were revealed for plasma ADA, GK, TP, and also for lymphocytic ADA, GK, DODH, PNP, TP, UDH, CDA. Plasma and lymphocytic adenosine deaminase as well as adenosine kinase activities were the most informative for minimal SSc activity detection, being a promising candidate marker. <h3>Conclusions</h3> The changes in enzymatic activity of purine and pyrimidine metabolism participate in pathogenesis of SSc. The enzymatic patterns studied can be used as auxiliary markers of SSc activity. The correction of purine and pyrimidine metabolism changes can be considered as one of the promising ways of increasing the effectiveness of SSc treatment. <h3>Reference</h3> [1] Guseva NG. Systemic scleroderma. M: Medicine1993;268. <h3>Disclosure of Interest</h3> None declared