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: 5.36). 01/1988; 139(11):3644-51.
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune-prone NZB and NZB × NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reated with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB × NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.
    Clinical Immunology and Immunopathology 01/1990; 53(3-53):475-487. DOI:10.1016/0090-1229(89)90009-3
  • [Show abstract] [Hide abstract]
    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 · 7.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.
    Autoimmunity 02/1992; 13(4):261-4. DOI:10.3109/08916939209112333 · 2.75 Impact Factor