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  • Title: Immune modulation during treatment of systemic sclerosis with plasmapheresis and immunosuppressive drugs.
    Author: Dau PC, Callahan JP.
    Journal: Clin Immunol Immunopathol; 1994 Feb; 70(2):159-65. PubMed ID: 8299231.
    Abstract:
    Immunologic effects of our previously reported treatment protocol were determined in eight systemic sclerosis (SSc) patients treated with plasmapheresis, cyclophosphamide, and prednisone as tolerated. Prior to treatment total serum IgG and circulating lymphocytes including the percentage of B, T, and NK cells were normal. Peripheral blood lymphocytes showed evidence of activation by increased spontaneous proliferation and expression of CD25 on T cells. In addition, CD4+ T cells showed increased expression of both activation (HLA-DR) and maturation (CD29) markers. The percentage of CD8+ T cells was low, resulting in a high CD4:CD8 T cell ratio. During treatment all patients showed clinical improvement. Laboratory testing showed that their NK cells had declined by 81%, B cells declined by 96%, and serum IgG declined by 49%; high titer ANA were abrogated. Total T cells declined by 52%, and the CD4:CD8 ratio fell to normal, due to an almost twofold increase in the percentage of CD8+ T cells. Spontaneous lymphocyte proliferation increased further and was accompanied by increased maturation and activation of both CD4+ and CD8+ T cells, as well as a reduction of immature CD4+ T cells. Among CD8+ T cells the percentage of cytotoxic cells increased as shown by an increase in the CD11b-, CD38+, and CD29+ phenotypes, a finding confirmed on follow-up three-color flow cytometry which showed an increase in activated CD8 cells bearing the cytotoxic CD28 marker. Three-color cytometry also showed that cells with the CD4+CD45RA+CD31+ suppressor inducer phenotype were low and those with the CD4+CD45RO+ CD31- helper inducer phenotype were high in treated SSc patients. Deficient CD4+CD45RA+CD31+ and CD8+ T cell populations suggest an immune regulatory imbalance in SSc which could have led to CD4+ T cell activation and autoimmunity. Depletion of B cells, in conjunction with augmentation of cytotoxic CD8+ T cells through combined therapy, may have diminished the autoimmune response.
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