CHARACTERIZATION OF INSULIN AUTOANTIBODIES IN RELATIVES OF PATIENTS WITH TYPE-I DIABETES

We studied in detail the anti-insulin autoantibodies in 29 nondiabetic relatives of patients with type I diabetes. The affinity of the autoa ntibodies for [I-125]human insulin was high (1.34 x 10(9)-20.71 x 10(9 ) L/mol), and the capacity was low (0.84 x 10(-12)-37.80 x 10(-12) M). The product of affinity x capacity of each relative's antibodies dire ctly correlated (r = 0.99) with the level of antibodies determined in our standard radioassay. The autoantibodies from each of the subjects studied had the same rank order of affinities for insulin from differe nt species. Guinea pig, fish insulin, and insulin containing Trp rathe r than Leu in position 13 of the A-chain inhibited minimally the human insulin binding. Human proinsulin, insulin containing Gln rather than Glu in position 17 of the A-chain, and desoctapeptide insulin (des B2 3-30) all inhibited binding effectively. Insulin autoantibodies in rel atives of patients with type I diabetes share common epitope(s), which suggests a common pathogenic mechanism for production of such antibod ies. The epitopes from this initial analysis appear to include amino a cids B1-B3 and A8-A13. The region recognized can be distinguished from the insulin receptor binding domain.