AB0494\u2005ACTIVITY OF PURINE AND PYRIMIDINE METABOLISM ENZYMES IN SYSTEMIC LUPUS ERYTHEMATOSUS: ENZYMATIC PATTERNS OF BLOOD PLASMA AND LYSED LYMPHOCYTES

Abstract

Background: Cytotoxic immunosuppressants are widely used nowadays for outcome improvement and better quality of life in severe systemic lupus erythematosus (SLE). As purine and pyrimidine metabolism suggest to be the major targets of most cytotoxic immunosuppressants, enzyme profiling of these metabolic pathways is recognized as an important step for a better balance between efficiency and safety in clinical practice. Objectives: To characterize enzymatic patterns of the major enzymes of purine and pyrimidine metabolic pathways in systemic lupus erythematosus. Methods: The research was carried out in agreement with the WMA Declaration of Helsinki principles. 50 adult SLE patients from the rheumatology unit of Volgograd Clinical Emergency Hospital #25 and 30 healthy controls were included in the study. Diagnosis of SLE had been established using ACR criteria (1997), and activity was assessed by means of ECLAM scale. Activities of 10 major enzymes involved in purine and pyrimidine metabolic pathways: adenosine deaminase (ADA; E.C. 3.5.4.4), adenosine kinase (AK; E.C. 2.7.1.20), guanylate kinase (GK; E.C. 2.7.4.8), dihydroorotate dehydrogenase (DODG; E.C. 1.3.5.2), IMP dehydrogenase (IMPDG; E.C. 1.1.1.205), purine nucleoside phosphorylase (PNP; E.C. 2.4.2.1), thymidine kinase (TK; E.C. 2.7.1.21), thymidine phosphorylase (TP; E.C. 2.4.2.4), uracil/thymidine dehydrogenase (UDG; E.C. 1.17.99.4), cytidine deaminase (CDA; E.C. 3.5.4.5) were measured in blood plasma and lysed lymphocytes. Results are expressed as mean±standard error. Statististical comparison tests are selected in line with common guidelines, differences were considered significant when p<0.05. Results: Enzymatic profiles in plasma of SLE patients are characterized by increased PNP, AK, UDG, IMPDG, CDA, TK, and DODG activities; ADA and GK were found to decrease. Lyzed lymphocytes are revealed however to increased AK, IMPDG, TK, as well as decreased PNP, ADA, GK, CDA, and TP activities. We have also found that most enzyme activities significantly correlate with ECLAM score in accordance with our previous results [1]. Plasma PNP, AK, UDG, IMPDG, CD, TK and DODG activities positively correlated with ECLAM score, as well as lymphocyte AK, IMPDG, and TK activities did. Negative correlations with ECLAM score were revealed for plasma ADA and TP, and also for lymphocyte PNP, ADA, GK, UDG, CD, TP, and DODG. Plasma PNP, AK, IMPDG, and lymphocyte PNP, ADA, AK activities had the closest relations with minimal SLE activity, being a candidate markers of it. Conclusion: The enzymatic patterns studied can be used as auxiliary markers of SLE activity, with special emphasis on minimal disease activity. References [1] Zborovskaya IA, Martemyanov VF, Zborovsky AB, et al. Purine nucleoside phosphorylase activity in rheumatic diseases. Ann Rheum Dis. 2009;68(Suppl3):764. Disclosure of Interests: None declared