Tuberculosis cutis colliquativa during long-term immunosuppressive therapy for rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to M Jendro.
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HLA genes have been identified as key genetic factors contributing to many chronic diseases characterized by autoimmune features. The role of HLA encoded molecules in the pathogenesis of these diseases is unresolved. We have now analysed soluble HLA-DR molecules circulating in the serum of patients with different autoimmune diseases and have defined parameters controlling serum levels. Patients with HLA-DR associated diseases were characterized by elevated serum concentrations of HLA-DR molecules and were clearly distinct from patients with HLA-B27 associated disorders. We did not find evidence for a correlation between disease activity, laboratory abnormalities and elevated serum concentrations of soluble HLA-DR molecules. Studies in normal individuals indicated that soluble HLA-DR molecules are at least partially regulated by the HLA haplotype. Highest serum concentrations were found in individuals carrying the HLA-DR3 or HLA-DR4 haplotype raising the possibility that the phenomenon of HLA-disease association reflects differences in the genetic control of soluble HLA-DR molecules. Interferon-gamma treatment caused an increase in serum concentrations of soluble HLA-DR molecules, whereas a decrease of circulating HLA-DR molecules was associated with an immunosuppressive with cyclosporine A. These data suggest that the patient's immunoresponsiveness represents a second important mechanism controlling circulating HLA-DR molecules.
HLA molecules are highly polymorphic glycoproteins with a single binding site for immunogenic peptides. The complex formed by HLA-DR molecules and peptides is the entity specifically recognized by the antigen receptor of CD4+ helper T lymphocytes. This biological function has been linked to the constitutive cell surface expression of HLA molecules on antigen-presenting cells which provide immunogenic peptides through denaturation or fragmentation of antigen. Here, we report that HLA-DR molecules can be identified in a soluble form circulating in the serum. Biochemical characterization and recognition of such soluble HLA-DR molecules by a monoclonal antibody reactive to conformational determinants on the alpha-beta HLA complex indicates that they are circulating as intact heterodimers. Upon activation, human T cells and B cells release soluble HLA-DR molecules. The expression and secretion of HLA-DR by T lymphocytes is greatly enhanced in the presence of macrophages indicating that the production of HLA-DR molecules might be regulated and controlled through factors derived from antigen-presenting cells. An alloreactive human T cell clone can be stimulated to proliferate in response to soluble HLA-DR molecules purified and enriched from serum suggesting that the soluble form of the natural ligand of the T cell receptor might have immunoregulatory functions.
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