The Effect of Anti-B-cell Therapy on the Development of Atherosclerosis in Patients with Rheumatoid Arthritis

Diana      S. Novikova; Tatyana      V. Popkova; Eugeny      L. Nasonov

doi:10.2174/138161212799504768

Abstract

Accelerated development of atherosclerosis (AT) in rheumatoid arthritis (RA) stems from common immune-inflammatory mechanisms underlying the diseases. While the key role of activation of the T-cell immune system component is considered to be proved, the role of B-lymphocytes has been investigated insufficiently. Earlier experimental models demonstrated the “atheroprotective” role of B-cells. At the same time, AT development is associated with activation of the B-cell immune system component and manifested by hyperproduction of antibodies to oxidized low density lipoproteins (oxLDL), heat shock proteins, etc. Wide applications of anti-B-cell therapy stimulate active research on effects of B-lymphocytes and their depletion on AT development in RA patients that have a high risk of cardiovascular events (CVE). Experimental models demonstrated that depletion of B2 cells instead of B1 cells under anti-CD20 treatment resulted in a slower development and progression of AT. Research on cardiovascular effects of chimeric antiCD20 monoclonal antibody (rituximab, RTX) in RA is definitely of high interest. Use of RTX in a combination with methotrexate does not increase the risk of serious side effects, including CVE, compared with the sole use of methotrexate. Currently, only few pilot research reports on favorable effects of RTX on the lipid profile and endothelial function in RA patients have been published. According to other authors, the frequency of CVE in RA patients receiving RTX therapy was somewhat higher than that in patients not treated with RTX. In rare cases such side effects as hypotension and arrhythmia were reported under RTX infusion. In addition, investigation of the combined use of statins and RTX is important, since some data are available on a reduced efficacy of RTX when administered with statins. Therefore, further research is required to clarify the role of the B-cell immune system component in AT development and the impact of anti-B cell therapy on the pathogenetic mechanisms of AT and CVE in RA patients.

Keywords: B-cell, B-cell depletion, rituximab, rheumatoid, atherosclerosis, statins, oxidized low density lipoproteins (oxLDL), heat shock proteins, cardiovascular events (CVE), methotrexate