title: Treatment of myasthenia gravis with anti-CD4 antibody: improvement correlates to decreased T-cell autoreactivity.
abstract: We treated a patient with severe myasthenia gravis with a chimeric (murine/human) anti-CD4 monoclonal antibody (cM-T412) for 7 days and followed the therapeutic effect by standardized muscle function tests, single-fiber electromyography, and immunologic examinations of disease-specific B- and T-cell functions. Clinical and electrophysiologic improvement began within 4 days, lasted for 3 months, and was maximal between days 16 and 58. The CD4+ lymphocytes decreased to a minimum of 80 cells per microliters of peripheral blood, recovered slowly during the first year of follow-up, and did not correlate with changes in disease severity. T-cell stimulation by human acetylcholine receptor was abolished by the treatment but became detectable at the time of worsening of symptoms. The concentration of acetylcholine receptor antibodies in serum was not decreased by the treatment. The results suggest that anti-CD4 antibody administration could be effective in the treatment of severe myasthenia gravis and indicate that acetylcholine receptor-specific T lymphocytes might contribute to the disturbed neuromuscular transmission in the disease.
authors.affiliation: Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Ahlberg
authors.forename: Q
authors.initials: Q
authors.lastname: Yi
authors.forename: R
authors.initials: R
authors.lastname: Pirskanen
authors.forename: G
authors.initials: G
authors.lastname: Matell
authors.forename: C
authors.initials: C
authors.lastname: Swerup
authors.forename: E P
authors.initials: EP
authors.lastname: Rieber
authors.forename: G
authors.initials: G
authors.lastname: Riethmüller
authors.forename: G
authors.initials: G
authors.lastname: Holm
authors.forename: A K
authors.initials: AK
authors.lastname: Lefvert
mesh_terms: D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy*; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D011950:Receptors, Cholinergic