LAUSR

Background The systemic scleroderma (SSc) is connective tissue disease of unknown cause. The key points in development of SSc are the increased number of high collagen-producing fibroblasts in the skin, endothelial dysfunction and immune activation. Recent studies report various metabolic disturbances in SSc patients. Purine and pyrimidine metabolic pathways are underlies the central processes of cellular life. The changes in activity of purine and pyrimidine metabolism enzymes in blood plasma and lysed lymphocytes depending on the SSc activity were described by us earlier [1]. At the same time, there are publications that confirm the relationship between changes in ADA activity in red blood cells and pronounced immune disorders [2]. Objectives to characterize enzymatic patterns of the major purine and pyrimidine metabolic pathways enzymes in lysed red blood cells depending on the SSc activity. Methods 51 SSc patients and 30 healthy controls were enrolled in the study. The diagnosis was verified in accordance with the international standards (ACR/EULAR 2013). Disease activity was assessed in accordance with the national classification [3]. 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; DC 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 lysed red blood cells. Results Mean age of patients (Mean± SD) was 42.8±1.3years, mean SSc duration was 7.9±0.7 years. We revealed substantial changes in enzymatic activities related to both purine and pyrimidine metabolism in lysed red blood cells of SSc patients. The increased ADA (p<0,001), AK (p<0,001), IMPDH (p<0,001), TK (p<0,001), UDH (p<0,001) activities and the decreased DODH (p<0,001), PNP (p<0,001) activities in lysed red blood cells were observed of SSc patients in comparison with healthy controls. AK, IMPDH, TK, UDH activities positively correlated with SSc activity. Negative correlations with SSc activity were revealed for ADA, CDA, DODG, GK, PNP, TP activities. Conclusion The progression of SSc goes with the imbalance of the purine and pyrimidine enzymes in a regular manner. Activity of the autoimmune inflammation is the factor that underlies the enzymatic pattern of purine and pyrimidine metabolism. References [1] Mozgovaya E., Bedina S., Trofimenko A., Zborovskaya I. The association between activity of purine and pyrimidine metabolism enzymes and disease activity in systemic scleroderma patients. Annals of the Rheumatic Diseases2018;77(2):1280. [2] Cowan M.J., Brady R.O., Widder K.J. Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1986Feb;83(4):108. [3] Guseva N.G. Systemic scleroderma. M.: Medicine,1993.268 p. Disclosure of Interests None declared