Purine metabolism and Multiple Sclerosis: different pattern according to different disease stage and different clinical form.

Abstract

P422 Purine metabolism and multiple sclerosis: pattern varies according to disease stage and clinical form G. Salemi, M. Gueli, V. Cusimano, M. Lo Re, V. Lo Re, M.A. Mazzola, S. Realmuto, P. Ragonese, G. Savettieri University (Palermo, IT) Background: Serum concentration of uric acid (sUA) was variably associated with Multiple Sclerosis (MS). Many papers reported lower sUA in MS patients respect to healthy controls, expecially in course of relapse. This lower sUA was considered as a marker of oxidative stress. However, this association was not confirmed by many other papers. Recently, an increase in the concentration of sUA, hypoxanthine, xanthine, and sum of oxypurine (sPU) was reported in a population of MS patients by HPLC detection. The authors suggested that this could be an index of a sustained purine catabolism, possibly due to imbalance in ATP homeostasis. Objective: To compare sUA and sPU between MS during stable disease and healthy controls. To confront sUA and sPU among different MS subtypes. To search for modification of sUA and sPU during and after a clinical relapse. Materials and Methods: We included MS patients with relapsing- remitting MS (RRMS), secondary-progressive MS (SPMS), and primary-progressive MS (PPMS) during stable disease and a group of healthy controls comparable for gender and age. Venous blood samples were obtained and the concentration of purine compounds was determined by HPLC separation. Moreover, subjects with MS were identified in course of a clinical relapse. Blood samples were obtained within two days from the onset, after 30 and 60 days and processed by HPLC. Non parametric tests were used to compare results between the groups. Results: We included 94 MS patients (74 RRMS, 14 SPMS, 6 PPMS) and 94 healthy controls. Median serum xanthine (p = 0.002), sUA (p = 0.0004) and sPU (p = 0.0002) concentrations were higher in MS sample. In RRMS median hypoxanthine concentration was lower respect to SPMS (0.002) and PPMS (0.01), while median sUA (p = 0.004) and sPU (p = 0.005) concentration was higher than in SPMS. Ten patients were included in course of a clinical relapse. No significant changes in the concentration of sUA aor sPU were observed comparing the first days after a relapse and the period post-relapse. Conclusion: Our data support the thesis that the changes at sUA and sPU observed in course of MS could be an index of a sustained purine catabolism, possibly due to imbalance in ATP homeostasis.