Organ-specific autoantibodies in HLA genotyped insulin-dependent diabetes mellitus families

The prevalence of cytoplasmic islet cell antibodies (ICA) and extrapancreatic antibodies (EPA), (stomach, adrenal and thyroid) was investigated in 132 juvenile onset diabetic patients, without personal or familial history of other autoimmune disease, and their 31 diabetic and 402 non-diabetic first degree relatives. The prevalence of ICA was 59% in index cases and 12% in the non-affected first degree relatives. The frequency of EPA was 23% and 16% respectively. There were no sex-related differences among the patients. However, among the non-affected relatives, an increased frequency of EPA was observed in females (23%) compared to males (8%) (P less than 10-4). There was a higher prevalence of ICA in healthy relatives bearing DR3 and/or DR4 antigen combinations compared to non-DR3 and non-DR4 individuals (14% versus 5%, P less than 0.05). Furthermore, ICA were more frequent in healthy siblings sharing two haplotypes compared with one or no haplotype (21% vs 10%, P less than 0.05). These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background.