Limited loss of tolerance to islet autoantigens in ICA+ first degree relatives of patients with type I diabetes expressing the HLA DQB1*0602 allele

被引:20
作者
Gianani, R
Verge, CF
MoromisatoGianani, RI
Yu, L
Zhan, YJ
Pugliese, A
Eisenbarth, GS
机构
[1] UNIV COLORADO, HLTH SCI CTR, BARBARA DAVIS CTR CHILDHOOD DIABET, DENVER, CO 80262 USA
[2] UNIV MIAMI, SCH MED, DIABET RES INST, MIAMI, FL USA
关键词
DQB1*0602 allele; GAD; IA-2; insulin autoantibodies; ICA;
D O I
10.1006/jaut.1996.0058
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 1996 Academic Press Limited
引用
收藏
页码:423 / 425
页数:3
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