Effects of rituximab in two patients with dysferlin-deficient muscular dystrophy

BACKGROUND: The administration of rituximab (RTX) in vivo results in B-cell depletion, but evidence for multiple mechanisms of action have been reported. Surprisingly, B cell depletion produced a response in patients with polymyositis, which is characterized as a T cell-mediated autoimmune disorder with biopsy findings similar to Miyoshi myopathy (MM). Indeed, in dysferlinopathies, there is evidence of immune system involvement including the presence of muscle inflammation and a down regulation of the complement inhibitory factor, CD55. METHODS: Two patients were treated with four weekly infusions of RTX 375 mg/m2. To measure the improvement in muscle strength after treatment, the isometric hand grip maximal voluntary contraction (MVC) was measured by load cell four times during treatment, and again after one year. In order to assess the reproducibility of our grip assessment, we determined the hand MVC analysis in 16 healthy subjects. Moreover, we measured the number of B cells present in patients by flow cytometric analysis during the course of treatment. RESULTS: The analysis of B cell number during the course of treatment showed that CD20- and CD19-positive cells were depleted to 0-0.01%. The decrease in B cells was followed by an improvement in the mobility of the pelvic and shoulder girdles as shown by the MRC%. The MVC values of both patients began at values lower than normal whereas during treatment patients had improved percentage of muscle strength. The strength peak in both patients coincided with the minimum B cell values. There were no severe adverse events associated with an infusion of RTX. CONCLUSION: We consider the increase in muscle strength observed in both treated patients to be a consequence of their treatment with RTX. To our knowledge, these are the first cases of increased muscle strength in patients with MM. Furthermore, the results of this study indicate that B cell depletion with RTX may be useful in the treatment of patients affected by MM, suggesting a possible role for B cells in the pathophysiology of this muscle disorder.