Anti-CD20 treatment is not the holy grail for treating autoimmune disease. #MSResearch #MSBlog #ResearchSpeak
"The Type 1 diabetologists are way ahead of us in that they have a very good idea of what autoantigens are driving their disease. The study below shows that B cell depletion with rituximab in type 1 diabetes only has a temporary impact on autoimmune B cell responses. The autoreactive cells bounce back quickly post-rituximab treatment. In short anti-CD20 therapies are not the holy grail when it comes to treating autoimmunity. This would be consistent with the experience of anti-CD20 therapies in MS and makes a case for using anti-CD20 treatments as a maintenance treatment, i.e. given continuously, rather than an induction treatment. The real questions that will be need to be answered ASAP; does maintenance anti-CD20 treatment prevent progressive MS?"
Epub: Chamberlain et al. Rituximab does not reset defective early B cell tolerance checkpoints. J Clin Invest. 2015 Dec 7. pii: 83840. doi: 10.1172/JCI83840.
Background: Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti-B cell therapy thwarts autoimmunity in these pathologies.
Objective: Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints.
Results: We found that anti-B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion.
Conclusions: We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.
Labels: anti-CD20, CD20, Immune tolerance, ResearchSpeak, type 1 diabetes