Abstract
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.
Original language | English (US) |
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Pages (from-to) | 423-425 |
Number of pages | 3 |
Journal | Journal of Autoimmunity |
Volume | 9 |
Issue number | 3 |
DOIs | |
State | Published - Jun 1996 |
Keywords
- DQB1*0602 allele
- GAD
- IA-2
- ICA
- Insulin autoantibodies
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy