Immunomodulation during treatment of polymyositis with plasmapheresis and immunosuppressive drugs.
Immunologic studies were carried out in a patient with polymyositis (PM), who showed increasing muscle strength and decreasing serum creatine phosphokinase levels during 20 weeks of treatment with plasmapheresis in conjunction with prednisone and cyclophosphamide. After an initial rise, serum IgG declined with treatment. Natural killer (NK) lymphocytes were reduced by 74%, B cells by 95%, and T cells by 38%. Spontaneous proliferation of peripheral blood mononuclear cells increased dramatically. Within the CD4+ T cell subset there was increasing maturation as shown by a rise in percent mature (CD29+) cells and reciprocal decline of immature (CD45RA+) cells. At the same time CD4+ T cells became increasingly activated as shown by HLA-DR expression. The percentage of CD8+ T cells increased strongly with treatment, and they showed increased activation and expression of the cytotoxic CD29+ and CD11b- phenotypes. CD8+ T cells exhibiting CD45RA or CD11b+ suppressor phenotypes were overall unchanged; however, on follow-up a proportion of CD8+ cells expressed the activated suppressor effector (CD11b-CD28-) phenotype. In addition to control of PM by the possible deletion of activated autoreactive B and T lymphocyte clones with cyclophosphamide, the activation and maturation of CD4+ T cells during treatment may have downregulated the autoreactive disease process, either through direct antiidiotypic suppression or by induction of the observed increase in cytotoxic and suppressor CD8+ T cells.
Dau
P C
PC
Department of Medicine, Evanston Hospital, IL 60201.
D000328:Adult; D016516:CD4-CD8 Ratio; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000032:analysis; D010725:Phosphocreatine / Q000097:blood; D010956:Plasmapheresis; D017285:Polymyositis / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D007166:Immunosuppressive Agents; D010725:Phosphocreatine; D017493:Leukocyte Common Antigens