TREATMENT OF MYASTHENIA-GRAVIS WITH ANTI-CD4 ANTIBODY - IMPROVEMENT CORRELATES TO DECREASED T-CELL AUTOREACTIVITY

We treated a patient with severe myasthenia gravis with a chimeric (mu rine/human) anti-CD4 monoclonal antibody (cM-T412) for 7 days and foll owed the therapeutic effect by standardized muscle function tests, sin gle-fiber electromyography, and immunologic examinations of disease-sp ecific B- and T-cell functions. Clinical and electrophysiologic improv ement began within 4 days, lasted for 3 months, and was maximal betwee n days 16 and 58. The CD4+ lymphocytes decreased to a minimum of 80 ce lls per mu 1 of peripheral blood, recovered slowly during the first ye ar of follow-up, and did not correlate with changes in disease severit y. T-cell stimulation by human acetylcholine receptor was abolished by the treatment but became detectable at the time of worsening of sympt oms. The concentration of acetylcholine receptor antibodies in serum w as not decreased by the treatment. The results suggest that anti-CD4 a ntibody administration could be effective in the treatment of severe m yasthenia gravis and indicate that acetylcholine receptor-specific T l ymphocytes might contribute to the disturbed neuromuscular transmissio n in the disease.