ALTHOUGH DR3-DQB1-ASTERISK-0201 MAY BE ASSOCIATED WITH MULTIPLE COMPONENT DISEASES OF THE AUTOIMMUNE POLYGLANDULAR SYNDROMES, THE HUMAN-LEUKOCYTE ANTIGEN DR4-DQB1-ASTERISK-0302 HAPLOTYPE IS IMPLICATED ONLY IN BETA-CELL AUTOIMMUNITY

Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed usi ng a PCR-based sequence-specific priming technique in 16 patients with autoimmune polyglandular syndrome type I(APS-I), 31 patients with APS -II, and 110 patients with component diseases of APS-II, including 9 p atients with isolated Addison's disease, 43 patients with Hashimoto's thyroiditis, 22 patients with Graves' disease, and 36 patients with vi tiligo. No significant associations was observed between HLA and APS-I patients in our data set, nor was sharing of HLA haplotypes by siblin g pairs affected by APS I significantly different from the random expe ctation. Thus, HLA-DRB1 and -DQB1 genes are probably not involved in A PS-I. To delineate the associations between HLA-DRB1, DQB1, and APS-II , we analyzed APS-II patients with or without beta-cell autoimmunity [ i.e. insulin-dependent diabetes (IDD) and/or islet cell or glutamic ac id decarboxylase autoantibodies]. Our results suggest that the associa tion between DR4-DQB10302 and APS-II was entirely due to the presence of pancreatic p-cell autoimmunity, since this haplotype was otherwise not significantly associated with APS-II or with any other of its com ponent diseases. In contrast, the DR3-DQB10201 haplotype was associat ed not only with IDD, but also with APS-II in the absence of pancreati c p-cell autoimmunity, as were several its component diseases, includi ng isolated Addison's disease, Graves' disease, and Hashimoto's thyroi ditis. Interestingly, the frequency of DQB10602, a dominantly protect ive allele against IDD, was not significantly decreased in the APS-II patients with IDD or p-cell autoimmunity, albeit the patient numbers w ere small. This phenomenon may suggest that the development of autoimm unity to nonpancreatic endocrine glands may predispose autoimmunity to the pancreatic p-cells and involve genes other than those of the MHC.