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Objective. To test the hypothesis that B cells play a role in the pathophysiology of dermatomyositis (DM) by examining the effect of B cell depletion in patients with symptomatic DM. Patients were treated with rituximab, a CD20؉ B cell-depleting monoclonal antibody.Methods. This was an open-label uncontrolled pilot trial in 7 adult patients with DM, 6 of whom had longstanding illness that was responding inadequately to a number of currently available immunosuppressive agents. All patients received 4 intravenous infusions of rituximab given at weekly intervals. Patients were followed up for up to 1 year without further treatment with rituximab. One patient was lost to followup. The principal efficacy outcome was muscle strength, measured by quantitative dynomometry.Results. All 6 evaluable patients exhibited major clinical improvement, with muscle strength increasing over baseline by 36-113%. Maximal improvements in muscle strength occurred as early as 12 weeks after the initial infusion of rituximab. CD20؉ B cells were effectively depleted in all patients by 12 weeks. Four patients experienced a return of symptoms that coincided with the return of B cells before the 52-week end point. Two patients maintained their increased muscle strength at 52 weeks, and 1 of these patients maintained this strength even after the return of B cells. Other symptoms of DM, including rash, alopecia, and reduced forced vital capacity, improved markedly in patients with these symptoms. Rituximab was well tolerated, with no treatment-related severe or serious adverse events during the observation period of this study. Conclusion.This small open-label study of DM patients treated with rituximab provided sufficiently encouraging results to justify a more formal evaluation of the value of B cell depletion therapy in the treatment of DM.

Objectives: Polyneuropathies with associated serum IgM antibodies are often difficult to treat. Rituximab is a monoclonal antibody directed against the B cell surface membrane marker CD20. Rituximab eliminates B cells from the circulation, and, over time, could reduce cells producing autoantibodies. This study tested the ability of rituximab to produce changes in serum antibody titres, and improvement in strength, in patients with neuromuscular disorders and IgM autoantibodies. Methods: Over a period of two years, the authors evaluated changes in strength, measured by quantitative dynamometry, and concentrations of several types of serum antibodies in patients with polyneuropathies and serum IgM autoantibodies. Twenty one patients treated with rituximab were compared with 13 untreated controls. Results: Treatment with rituximab was followed by improved strength (an increase of mean (SEM) 23% (2% )of normal levels of strength), a reduction in serum IgM autoantibodies (to 43% (4%) of initial values), and a reduction in total levels of IgM (to 55% (4%) of initial values). There was no change in levels of serum IgG antibodies. There were no major side effects, even though B cells were virtually eliminated from the circulation for periods up to two years. Conclusions: In patients with IgM autoantibody associated peripheral neuropathies, rituximab treatment is followed by reduced serum concentrations of IgM, but not IgG, antibodies, and by improvement in strength. Additional studies, with placebo controls and blinded outcome measures, are warranted to further test the efficacy of rituximab treatment of IgM associated polyneuropathies.

Hel-N1, a human RNA-bindlng protein, shares significant homology with Drosophila protein ELAV, which is essential for fly neuronal development. Het As a means to identify cellular RNA targets for these proteins, we devised combinatorial shape libraries representing naturally derived 3' untranslated regions and were able to select a structurafly related subset of transcripts that bound to HBe-N1.