Treatment with the anti-CD20 monoclonal antibody rituximab mitigates gonadal disruptions in the collagen-induced arthritis in male DBA/1 J mouse model

Rheumatoid arthritis (RA), which is driven by persistent activation of the immune system, primarily affects the joints. Several reports have estimated the risk of gonadal disruptions in arthritic patients, with potential attributable risk factors such as treatments with the disease-modifying antirheumatic drugs and the influence of the disease itself. The FDA approved rituximab, a therapy for non-Hodgkin's lymphoma, for management of RA in February 2006. However, the influence of repeated treatment with rituximab on gonadal function in RA has not been reported yet. Thus, the aim of the presents study is to evaluate whether repeated treatment with the clinically relevant dose of rituximab may change the gonadal disruptions in collagen-induced arthritis in male DBA/1 J mouse, a model of RA. Testicular disruptions, as determined by the sperm DNA strand breaks, sper-matocyte chromosomal analysis and spermiogram examination have been conducted by the use of standard techniques. Additionally, we aimed to test whether the anti-rheumatic effect of rituximab also decreases the cellular oxidant-antioxidant imbalance in arthritic male DBA/1 J mice. Repeated treatment of naive control DBA/1 J mice with rituximab did not exhibit any significant deleterious effects. Moreover, repeated adminis-tration of rituximab to the arthritic DBA/1 J mice suppressed disease severity and decreased testicular disrup-tions. Rituximab treatment also diminished gonadal oxidative stress, through decreasing reactive oxygen species generation and restoring the reduced glutathione level in arthritic DBA/1 J mice. In conclusion, rituximab is a safe therapeutic agent and can mitigate gonadal disruptions induced by arthritis, which insinuates the impor-tance for arthritic patients especially at reproductive age.

Automated summary

This study aimed to evaluate the effect of repeated rituximab treatment on gonadal disruptions in a mouse model of rheumatoid arthritis (RA) and found that repeated administration of rituximab can alleviate the severity of arthritis and testicular disruptions, while reducing oxidative stress.