Increased expression of HLA-DR molecule on peripheral blood Th lymphocytes from patients with IgA nephropathy

Abstract

Background. IgA nephropathy is the commonest type of glomerulonephritis. Recent studies have shown a decrease in the expression of HLA class I antigens on peripheral blood mononuclear leukocytes (PBML) from patients with HLA class II-associated autoimmune diseases. In this study, the expression of HLA molecules on T cells from patients with IgA nephropathy was examined in order to investigate the immunological events contributing to the pathogenesis of this disorder. Methods. Thirty Japanese patients with IgA nephropathy were studied. Nine patients with membranous nephropathy and 21 sex-and age-matched healthy individuals were enrolled as controls. Heparinized PBML with or without stimulation by an anti-CD3 monoclonal antibody were analyzed in regard to the expression of HLA-class I, HLA-DR, CD4, CD8, CD11a, CD11b, and CD56, by two-color fluorescence flow cytometry. Results. The expressions of HLA-class I, HLA-DR, CD11a, CD11b, and CD56 on resting CD3-positive, CD4-positive, CD8-positive, or CD20-positive cells from patients with IgA nephropathy were found to be comparable with those from the controls. However, after stimulation by anti-CD3 antibody, the expression of HLA-DR on CD4-positive cells from these patients was significantly higher than that from the controls. Further, the expression of HLA-DR on CD4-positive cells from patients with proteinuria of more than 1 g/day was much higher than that in patients with proteinuria of less than 1 g/day. Conclusions.In this study, the expression of HLA-DR on stimulated Th cells from IgA nephropathy patients was shown to be significantly higher than the expression in the stimulated T cells from the controls. This finding suggests that Th cells may acquire antigen-presenting activity by HLA-DR expression, present antigens to other Th cells, promote B cells to produce antibodies, and, presumably, lead to the development of IgA nephropathy.