AUTOANTIBODIES TO INSULIN AND TO PROINSULIN IN TYPE-1 DIABETIC-PATIENTS AND IN AT-RISK PROBANDS DIFFERENTIATE ONLY LITTLE BETWEEN BOTH ANTIGENS

To answer the question whether insulin or proinsulin would be the true antigen for both insulin and proinsulin autoantibodies, displacement experiments of I-125-insulin and -proinsulin binding with both unlabel ed antigens were performed in sera of four groups of antibody-positive probands: first-degree relatives of Type 1 diabetic patients, pre-Typ e 1 diabetic persons, recent-onset Type 1 diabetic patients, insulin-t reated Type 1 diabetic patients. In subjects who were primarily screen ed to constitute these groups, prevalences of insulin and proinsulin a utoantibodies were nearly identical. In antibody-positive sera, I-125- insulin and -proinsulin binding values in general were closely correla ted to each other with regression coefficients near 1.0. In all groups of probands, mean values of I-125-insulin and -proinsulin binding did not significantly differ. With the exception of a few sera, insulin a nd proinsulin antibodies differentiated only little between both antig ens. Epitopes of the insulin molecule are therefore preferred. Neverth eless, insulin and proinsulin autoantibodies are not completely identi cal nor are insulin autoantibodies merely a subgroup of proinsulin aut oantibodies: In each group, in the mean, insulin antibodies as well as proinsulin antibodies reacted somewhat (but significantly) stronger w ith their respective antigen. In some cases a distinct (relative) spec ificity for either antigen of insulin and proinsulin autoantibodies we re observed, the latter being still present after some months of insul in treatment. In conclusion, despite detectable differences in antigen specificity, insulin and proinsulin autoantibodies seem to be equally potent markers of Type 1 diabetes mellitus.