Abstract:Anti‐idiotypic antibodies are antibodies that are directed against the variable region of the corresponding antibody molecule and have been postulated to have a regulatory role in the immune response. Circulating anti‐idiotypic antibodies have been reported in several antibody‐mediated autoimmune diseases.We have established the following detection system for anti‐idiotypic antibodies in human anti‐glomerular basement membrane (GBM) disease. Spleen cells harvested from BALB/c mice immunised with human GBM were incubated with GBM‐coated sheep red blood cells in the presence of guinea pig complement. Each spleen cell that produced anti‐GBM antibodies resulted in a surrounding plaque where antibodies lysed the GBM‐coated RBC. The number of plaques could be inhibited by the addition of heterologous anti‐idiotypic antibodies to the plaquing mixture. Anti‐idiotypic antibodies were then sought in both acute and convalescent phase sera from patients with anti‐GBM disease and in laboratory staff who repeatedly handled GBM and sera containing anti‐GBM antibodies. Anti‐GBM antibodies were removed from all material before testing and affinity‐purified preparations contained concentrations of IgG corresponding to the range that resulted in inhibition when affinity‐purified rabbit anti‐idiotypic antibody was examined.No anti‐idiotypic antibodies could be demonstrated in any of the sera or IgG preparations examined. We conclude that if circulating anti‐idiotypic antibodies are present in patients with anti‐GBM disease, they must be infrequent, or at concentrations below the limits of detection of this assay (<1 mcg/mL). The observations of anti‐idiotypic antibodies in other antibody