Idiotypic determinants on human anti-insulin antibodies are cyclically expressed

Insulin-treated diabetics develop a heterogeneous antibody response to the protein hormone. To understand the repertoire of this diverse immune response, we developed monoclonal antibodies (Mab) that recognize idiotypic determinants on anti-insulin antibodies. Two Mab that recognize distinct idiotopes on anti-insulin antibodies were studied in detail. These idiotopes were present on IgG, but not IgM, anti-insulin antibodies from the proband and from four of 11 insulin-treated diabetics. The determinants recognized were distinct from conventional allotype (Gm) markers and were found in both Type I and Type II diabetics. The partial inhibition of anti-idiotope binding by beef insulin suggests that idiotopes related to the binding site for beef insulin may be recognized. When the presence of idiotope-positive molecules was determined sequentially during insulin therapy, in one patient, idiotope expression was found to be cyclical. In contrast, the total amount of anti-insulin antibody was constant, whereas idiotope expression varied. These data suggest that common V region determinants are employed in the anti-insulin response, and their variable expression may reflect dynamic regulation during chronic insulin therapy.