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 β-cell autoimmunity

Wei Huang, Ellen Connor, Teresita Dela Rosa, Andrew Muir, Desmond Schatz, Janet Silverstein, Samuel Crockett, Jin-Xiong She, Noel K. Maclaren

Research output: Contribution to journalArticle

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Abstract

Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using a PCR-based sequence-specific priming technique in 18 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 β-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 β-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 β-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 β-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 β-cells and involve genes other than those of the MHC.

Original languageEnglish (US)
Pages (from-to)2559-2563
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number7
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

HLA Antigens
Autoimmunity
Haplotypes
Autoimmune Diseases
Medical problems
Insulin
Autoimmune Polyendocrinopathies
Addison Disease
Hashimoto Disease
Genes
Graves Disease
Glutamate Decarboxylase
Alleles
Autoantibodies
Endocrine Glands
Vitiligo
Islets of Langerhans
Siblings
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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 β-cell autoimmunity. / Huang, Wei; Connor, Ellen; Dela Rosa, Teresita; Muir, Andrew; Schatz, Desmond; Silverstein, Janet; Crockett, Samuel; She, Jin-Xiong; Maclaren, Noel K.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 7, 01.01.1996, p. 2559-2563.

Research output: Contribution to journalArticle

Huang, Wei ; Connor, Ellen ; Dela Rosa, Teresita ; Muir, Andrew ; Schatz, Desmond ; Silverstein, Janet ; Crockett, Samuel ; She, Jin-Xiong ; Maclaren, Noel K. / 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 β-cell autoimmunity. In: Journal of Clinical Endocrinology and Metabolism. 1996 ; Vol. 81, No. 7. pp. 2559-2563.
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abstract = "Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using a PCR-based sequence-specific priming technique in 18 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 β-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 β-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 β-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 β-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 β-cells and involve genes other than those of the MHC.",
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AU - Connor, Ellen

AU - Dela Rosa, Teresita

AU - Muir, Andrew

AU - Schatz, Desmond

AU - Silverstein, Janet

AU - Crockett, Samuel

AU - She, Jin-Xiong

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