Presence of shared idiotypes in serum and immune complexes in patients with IgA nephropathy

Abstract

Patients with IgA nephropathy often present a large array of antibodies against diet antigens and this disease can be experimentally induced by alimentary antigens. In this report, we have described the isolation from a patient with IgA nephropathy of antibovine serum albumin (BSA)-antibody idiotypes that are specifically recognized by auto-and heteroantiidiotypic antibodies. The fact that antigen (BSA) but not monomeric or aggregated human IgG inhibited the binding of antiidiotypic antibodies to the idiotypes, suggested that the idiotypic determinants are in or near the antigen binding site and that it is not a rheumatoid factor. By means of the heteroantiidiotypic antibodies raised in rabbits we observed the presence of increased levels of shared idiotypes in serum and/or immune complexes (IC) of 48 out of 70 (68.5%) genetically unrelated patients with IgA nephropathy. The close correlation (P less than 0.005) between the presence of IgA-IC, measured by Raji cell assay, and the existence of high levels of serum idiotypes, suggest that a portion of circulating IC could consist of idiotype-antiidiotype. A strong concordance between the presence and levels of idiotypes and the clinical activity, as defined by the existence of haematuria, was also noted. The discrepancies and absence of correlation observed in our study among the levels of anti-BSA antibodies of different classes and serum levels of idiotypes, circulating IC and haematuria could suggest that the antibodies reacting with the heterologous antiidiotypic antibodies could be directed to other more pathogenic antigens than dietary antigens. All together, our results suggest that IgA nephropathy might belong to the group of diseases that occur in susceptible individuals with a limited potential in the immunological response repertoire.