Identification of three major target molecules of IgM antilymphocyte autoantibodies in systemic lupus erythematosus
Division of Rheumatology and Immunology, University of North Carolina at Chapel Hill 27514. The Journal of Immunology
(Impact Factor: 4.92).
Three cell lymphocyte antigens of m.w. 55,000, 70,000, and 105,000 to 110,000 were identified by Western blotting as targets of IgM autoantibodies in serum from a group of 49 patients with systemic lupus erythematosus. The 55- and 70-kDa antigens were well expressed on unstimulated peripheral T cells, whereas the 105- to 110-kDa target was demonstrable only on mitogen-activated T cells and lymphoblastoid T cell lines. Localization of these molecules to the plasma membrane was established by cytoabsorption experiments in which IgM antibody staining of blotted antigens was specifically absorbed from systemic lupus erythematosus serum during 4 degrees C incubations with intact lymphocytes, and by their detection in purified lymphocyte plasma membranes. While the identity of these target antigens vis a vis known surface determinants was not defined, their expression on peripheral T cells from multiple donors and on cell lines of both undifferentiated (HSB-2) and phenotypically mature (Jurkat; HUT 78) types excluded alloantigens, major histocompatibility complex-encoded determinants, and most T cell differentiation antigens as candidates in this regard. Expression of the IgM autoantibody targets on HSB-2 cells argues against discrete T subset specificities as well. IgM reactivity with the 55-, 70-, and 105- to 110-kDa antigens by blotting was highly correlated with antilymphocyte antibody activity in complement-dependent cytotoxicity assays (Fisher's p less than 0.001), and paralleled flow microfluorimetric and microcytotoxicity quantitation of IgM antibody activity in serial observations of individual patients studied during different phases of disease activity. Taken together, these data suggest that IgM lymphocytotoxic antibodies in systemic lupus erythematosus are directed predominantly against a limited number of non-T cell subset-specific antigens.
Available from: jem.rupress.org
Journal of Experimental Medicine 10/1988; 168(4):1475-1480. DOI:10.1084/jem.168.4.1475 · 12.52 Impact Factor
Available from: PubMed Central
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ABSTRACT: Serum from patients with systemic lupus erythematosus (SLE) frequently contain IgM and IgG autoantibodies to the constitutively expressed 73-kD/pI 5.5 member of the hsp70 family of heat shock proteins, as determined by one-dimensional (SDS-PAGE) and two-dimensional (IEF/SDS-PAGE) immunoblotting, and by solid-phase SLE Ig immunoprecipitation experiments using hsp70 protein-specific mAbs as probes. Autoantibodies to hsp70 also were detected in a minority of sera from patients with other rheumatic or viral diseases, but not in normal sera. These data may provide additional insight into etiologic and pathophysiologic mechanisms in this and related autoimmune disorders.
Journal of Experimental Medicine 11/1988; 168(4):1475-80. · 12.52 Impact Factor
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ABSTRACT: In previous studies, we demonstrated that patients with active systemic lupus erythematosus (SLE) had significantly decreased percentages of circulating CD4+2H4+ suppressor/inducer cells. The decrease in this T cell subset was most frequent and most marked in patients with active SLE and renal disease. In the present study, we attempted to determine whether SLE patients had plasma antilymphocyte antibodies preferentially reactive with the CD4+2H4+ subset. We found that many SLE patients did have these specifically reactive antibodies. Furthermore, the presence of antilymphocyte antibodies reactive with CD4+2H4+ cells correlated with disease activity in these patients. Also, in vitro functional studies revealed that suppressor/inducer function was eliminated in the pokeweed mitogen-driven IgG synthesis system after the treatment of CD4 cells with patient plasma antilymphocyte antibodies and complement. These results suggest that antilymphocyte antibodies play a role in the elimination of CD4+2H4+ cells in patients with active SLE.
Arthritis & Rheumatology 04/1989; 32(4):398-405. DOI:10.1002/anr.1780320408 · 7.76 Impact Factor
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