Purpose Characterization of activity patterns of several mutually converting xanthine oxidoreductase subtypes, xanthine oxidase (XO) and xanthine dehydrogenase (XDG), within plasma and the blood cell compartments in systemic lupus erythematosus as compared with rheumatoid arthritis patients.

Methods The research was carried out in agreement with the WMA Declaration of Helsinki principles. 56 SLE patients and 77 RA patients were enrolled in this study. Diagnosis of SLE was verified using the ACR criteria (1997). RA was verified according to ACR/EULAR criteria (2010). Disease activity was assessed according to SLEDAI-2K and DAS28 indices, respectively. The reference group consisted of 35 healthy controls. Lymphocytes and erythrocytes were separated by means of density gradient centrifugation (1077 g/ml). XO and XDG activities were measured in plasma, lysed lymphocytes and lysed RBC using previously published kinetic techniques. Results were expressed as median and quartiles. Correlations were analyzed using Spearman’s correlation coefficient. Differences were considered significant when p<0.05.

Results Mean age of SLE patients was 35 (31; 42) years, mean duration of disease was 8 (5; 11) years. Mean age of RA patients was 45 (37; 49) years, mean RA duration was 8 (6; 10) years. 15 (26.8%) SLE patients had mild disease activity, 26 (46.4%) had moderate activity, and 15 (26.8%) had high activity. 16 (20.8%) RA patients had mild disease activity, 49 (63.6%) had moderate activity, and 12 (15.6%) had high activity. Both xanthine oxidoreductase subtypes had various activity shifts in plasma and lysed blood cells in RA as well as in SLE. Both SLE and RA patients had high plasma XO activity in combination with low plasma XDG activity (all p<0.05), while low XO and XDG activities were demonstrated in lysed lymphocytes for these two groups (all p<0.001). Lysed red blood cells in RA had high XO activity in combination with low XDG activity (all p<0.001). SLE patients were revealed low XDG activity without significant shift of XO activity in red blood cells. When comparing SLE and RA, SLE patients had lower plasma XDG (p=0.012), higher lymphocyte XO (p<0.001), lower erythrocyte XO (p<0.001), and lower erythrocyte XDG (p<0.001) activities. There was positive correlation between plasma XO activity and the disease activity index as well as negative correlations between plasma XDG activity, lymphocyte XO activity, lymphocyte XDG activity and the disease activity index both in SLE and RA (all p<0.001). Red blood cells in SLE had negative XO correlation and positive XDG correlation with disease activity; such correlation pattern in RA was inverse (all p<0.001).

Conclusion The imbalance between oxidase and dehydrogenase subtypes of xanthine oxidoreductase in SLE was expressed in higher levels of circulating XO activity that is responsible more for free radicals generation. A decrease of lymphocytic XO and XDG activities could be an indirect evidence of purine metabolism disturbance in SLE and RA. Increase of XO/XDG ratio in erythrocytes may affect the lifespan of these cells both in SLE and RA.