Background and purpose: Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real-life study. Method: Inclusion criteria were: age > 18 years; MG with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid-dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA-post-intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected. Results: Twenty-nine patients were included: 20 with anti-AChR MG, five with anti-MuSK MG and four with seronegative MG. MGFA-PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%). Conclusion: The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.
Cytotoxic T lymphocytes (CTL) which recognized measles virus antigens were generated by in vitro sensitization of peripheral blood lymphocytes from normal volunteers against autologous measles virus-infected lymphocytes. Cytotoxicity of measles virus-infected targets by these effectors was considerably enhanced when the effector-target cell mixtures were incubated in presence of 10 or 100 ng myelin basic protein (MBP) for the 3-hour duration of the 51Cr release assay. In most experiments, specific release of radioisotope was doubled or tripled. Bovine serum albumin caused only slight increases in cytotoxicity. The killing of allogeneic target cells by alloimmune CTL was not affected by either of these reagents. Measles-specific CTL were also able to kill target cells that were cultured overnight in presence of MBP but washed prior to the assay. Conversely, CTL generated by culturing lymphocytes in presence of MBP for 6 days were able to kill MBP-coated and measles virus-infected target cells. The implications of these findings in the pathogenesis of multiple sclerosis are discussed.
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