Why B cell Reduction doesn’t always work with MG Patients
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Rituximab: Why B cell reduction therapy doesn’t work for all MG patients

Rituximab: Why B cell reduction therapy doesn’t work for all MG patients

By Kevin O'Connor, PhD

Rituximab (brand name Rituxan) was originally developed to treat B-cell lymphoma. This therapeutic targets the cancerous B cells, eliminating them with remarkable efficiency. It has also been used to treat patients who have autoimmune diseases, including MG, though it is not FDA approved for MG and consequently used “off label.”

 

For a person with MG, the immune system is self-reactive, targeting and damaging the body’s own healthy tissue—in the case of MG, receptor sites at the neuromuscular junction. As patients know, this causes muscle weakness and fatigue. Disease-affecting autoantibodies, which target neuromuscular junction receptors in MG, are produced by B cells. Consequently, removing B cells is effective in reducing autoantibodies and lessening MG symptoms, thus allowing patients to lead more active lives.

 

As effective as the treatment is, nature finds a way to challenge us; rituximab works well in some patients, but not all. Specifically, patients with the MuSK form of MG have suffered relapses after completing a course of rituximab and getting their symptoms under control. Colleagues at Yale and I conducted research, published last year in JCI Insight, to find out why.

 

In our study, we looked at patients with MuSK MG who had suffered a relapse after treatment with rituximab. When we studied their blood, we found B cells that persisted despite the treatment. We were able to determine that these cells were not newly produced B cells, but clones of the patient’s B cells that had been present before treatment.  Essentially, the treatment puts out the flames, but the embers remain burning, and when you remove the treatment, the fire can light up again.

 

We don't yet know why these B cell clones persist in the body, but with a better understanding of why some patients with MG relapse, physicians can adjust courses of treatment accordingly or can apply new treatment options that may better reduce symptom burden.

 

*This article shares study results and is not meant to be medical advice. Talk to your physician if you have questions about how this study’s findings may affect your individual course of treatment.

 

Dr. Kevin C. O’Connor is an Associate Professor of Neurology and Immunobiology at Yale University School of Medicine and the Vice Chair of the MGFA Scientific Advisory Board.

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