Abstract
BackgroundThe 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.MethodsTwo 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.ResultsThe 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.ConclusionWe 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.
Highlights
The administration of rituximab (RTX) in vivo results in B-cell depletion, but evidence for multiple mechanisms of action have been reported
The two main phenotypes recognized in such conditions are Miyoshi myopathy (MM), a disorder that preferentially affects the distal musculature, and Limb-Girdle muscular dystrophy type 2B (LGMD2B), a disorder that is characterized by involvement of the pelvic and shoulder girdles [2]
Patients Data from 2 patients, both males aged between 30 and 40 years, were obtained. Both patients had a muscle disorder of long duration (15-20 years), and both were symptomatic with reduced muscle strength in the distal muscles of the lower limbs and above
Summary
The administration of rituximab (RTX) in vivo results in B-cell depletion, but evidence for multiple mechanisms of action have been reported. 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). Dysferlinopathies are recessive inherited muscular dystrophies caused by mutation of the dysferlin gene (DYSF) mapped to human chromosome 2p13 [1]. The two main phenotypes recognized in such conditions are Miyoshi myopathy (MM), a disorder that preferentially affects the distal musculature, and Limb-Girdle muscular dystrophy type 2B (LGMD2B), a disorder that is characterized by involvement of the pelvic and shoulder girdles [2]. The DYSF gene encodes a 230-kDa protein, which is normally expressed in the sarcolemma in skeletal muscle and. DYSF is expressed in cardiomyocytes, there is no evidence of cardiac muscle dysfunction in DYSF-deficient patients. Miyoshi myopathy is associated with markedly elevated creatine kinase levels (10 times normal) and dystrophic changes in muscle histopathology
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