Limited Loss of Tolerance to Islet Autoantigens in ICA+ First Degree Relatives of Patients with Type I Diabetes Expressing the HLA DQB10602 Allele

• Published in: Journal of autoimmunity Vol. 9; no. 3; pp. 423 - 425
• Main Authors: Gianani, R., Verge, C.F., Moromisato-Gianani, R.I., Yu, L., Zhang, Y.J., Pugliese, A., Eisenbarth, G.S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.1996
• Subjects: Adolescent; Adult; Aged; Alleles; Autoantibodies - blood; Autoantigens - immunology; Child; Child, Preschool; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; DQB10602 allele; Family Health; GAD; Glutamate Decarboxylase - immunology; HLA-DQ Antigens - genetics; Humans; IA-2; ICA; Immune Tolerance; Insulin - immunology; insulin autoantibodies; Islets of Langerhans - immunology; Middle Aged; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - immunology; Radioimmunoassay; GAD; insulin autoantibodies; ICA; DQB10602 allele; IA-2
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1996.0058

The DQB1*0602 allele confers dominant protection from Type I diabetes even among islet cell antibody positive (ICA+) first degree relatives of affected individuals. Lack of progression to diabetes in these subjects, despite ICA positivity, could be explained by a loss of tolerance limited to fewer islet autoantigens than in ICA+ relatives progressing to the disease. To test this hypothesis we have determined autoantibodies by radioassay to three islet autoantigens, glutamic acid decarboxylase (GAD), insulin and the novel neuroendocrine antigen ICA512/IA-2 in 84 HLA-typed ICA+ first degree relatives of patients with Type I diabetes. Among the eleven relatives expressing the 0602 allele (0602+) only two were positive for more than one antibody as determined by radioassay. In contrast, 55/73 ICA+ relatives lacking this allele (non-0602) expressed more than one autoantibody ( P<0.01). The prevalence of antibodies to GAD (GAA) was not significantly different in ICA+ relatives with and without the 0602 allele (7/11 in 0602+ versus 60/73 in non-0602). In contrast, anti-insulin antibodies (IAA) were present in only 2/11 0602+ ICA+ relatives versus 47/70 in non-0602 ICA+ relatives ( P<0.01). Similarly, only one individual carrying the 0602 allele was positive for ICA512 autoantibodies versus 33/70 in the non-0602 group ( P<0.01). These data indicate that even among ICA+ relatives the 0602 allele is associated with a limited immune response to islet antigens and amongst 0602+ relatives this response is mostly directed against GAD.