Lymphocytotoxic activity in primary glomerulonephritis: evidence for immune complex-mediated cytotoxicity

Sera from 84 patients with primary glomerulonephritis (GN) were tested for lymphocytotoxic activity (LCA) against panels of (a) normal peripheral lymphocytes and (b) B-lymphocytes obtained from patients with chronic lymphatic leukaemia (CLL). Significant LCA was found particularly in minimal change GN, acute post-streptococcal GN (AGN-PS) and mesangiocapillary GN (MCGN) where 62%, 75% and 45% respectively of samples were positive. No correlation was observed between LCA and levels of C3 or immune complexes. All but three positive sera showed reactivity against T and B cells; these three showed only T cell cytotoxicity. Fractionation of 6 sera (2 minimal change GN; 2 AGN-PS; 2 MCGN) on Sephadex G200 showed cell killing to reside in the exclusion peak. When samples were separated under dissociating conditions at pH 3.0, there was significant reduction in LCA (P less than 0.001) compared to that of fractions collected at pH 7.2. The same protocol did not affect the lymphocytotoxicity of anti-human lymphocyte globulin. The data suggest that lymphocyte killing in GN is mediated at least in part by antigen/antibody complex activity. The reaction is immunochemically similar to that seen in systemic lupus erythematosus and may have comparable implications for antibody regulation in GN.