Lymphocyte Xanthine Oxidoreductase: Activity vs Extraarticular Manifestations in Rheumatoid Arthritis

Study Objective: To study lymphocyte lysates for the dependence of the activity of xanthine oxidoreductase (XOR) complex: xanthine oxidase (XO) and xanthine dehydrogenase (XDG) — on the presence of extraarticular (systemic) manifestations (EAM) in patients with rheumatoid arthritis (RA). Study Design: Comparative study. Material and Methods. The study included 77 patients with verified RA (study group) and 35 apparently healthy subjects (control group). Lymphocytes were isolated using А. Böyum method in Lymphosep with a density gradient of 1.077–1.079 g/mL. Ferment activity was measured with kinetic methods and expressed in nM/min/mL equivalent to 107 cells per 1 mL. Study Results. XO reference range is 14.11–31.33 nM/min/mL; that of XDG — 18.62–39.64 nM/min/mL. For RA patients as a whole and patients with and without EAMs, lymphocytes demonstrated a significant reduction in the activity of both ferments vs controls (р < 0.001); in RA patients with EAMs, the XO and XDG activity was even lower (р < 0.001). Spearman correlation analysis identified the dependence of XO and XDG activity on the presence of EAMs: direct moderate correlations for XO (ρ = 0.6; p < 0.001) and XDG (ρ = 0.499; p = 0.000041). There is a strong direct correlation between XO and XDG activity, the intensity of which was higher where RA was associated with EAMs: (ρ = 0.72; p = 0.025) and (ρ = 0.87, p = 0.004) for RA only with articular involvement and for RA with EAMs, respectively. Conclusion. In lymphocytes of patients with RA, we found some changes in the XOR enzyme profile, the intensity of which depends on the presence of EAMs in the clinical presentation of the disease. Where XO activity is below 10.86 nM/min/mL and/or with XDG activity below 14.31 nM/min/mL, it is assumed that RA patients have EAMs. It is then recommended that the patient undergoes a comprehensive examination for early EAM identification and therapy adjustment. Keywords: rheumatoid arthritis, lymphocytes, xanthine oxidoreductase, xanthine oxidase, xanthine dehydrogenase.