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
W Huang, E Connor, TD Rosa, A Muir, D Schatz, J Silverstein, S Crockett, JX She and NK Maclaren
Department of Pathology, University of Florida College of Medicine, Gainesville 32610, USA.
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.
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