Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity.
Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using 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 patients with isolated Addison's disease, 43 patients with Hashimoto's thyroiditis, 22 patients with Graves' disease, and 36 patients with vitiligo. No significant associations was observed between HLA and APS-I patients in our data set, nor was sharing of HLA haplotypes by sibling pairs affected by APS I significantly different from the random expectation. Thus, HLA-DRB1 and -DQB1 genes are probably not involved in APS-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 acid decarboxylase autoantibodies]. Our results suggest that the association between DR4-DQB1*0302 and APS-II was entirely due to the presence of pancreatic beta-cell autoimmunity, since this haplotype was otherwise not significantly associated with APS-II or with any other of its component diseases. In contrast, the DR3-DQB1*0201 haplotype was associated not only with IDD, but also with APS-II in the absence of pancreatic beta-cell autoimmunity, as were several its component diseases, including isolated Addison's disease, Graves' disease, and Hashimoto's thyroiditis. Interestingly, the frequency of DQB1*0602, a dominantly protective allele against IDD, was not significantly decreased in the APS-II patients with IDD or beta-cell autoimmunity, albeit the patient numbers were small. This phenomenon may suggest that the development of autoimmunity to nonpancreatic endocrine glands may predispose autoimmunity to the pancreatic beta-cells and involve genes other than those of the MHC.
Huang
W
W
Department of Pathology, University of Florida College of Medicine, Gainesville 32610, USA.
Connor
E
E
Rosa
T D
TD
Muir
A
A
Schatz
D
D
Silverstein
J
J
Crockett
S
S
She
J X
JX
Maclaren
N K
NK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002648:Child; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology*
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains