High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them

Wei Huang, Jin-Xiong She, Andrew Muir, Danuta Laskowska, Barbara Zorovich, Desmond Schatz, Noel K. Maclaren

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Although HLA class II genes are important in insulin-dependent diabetes (IDD), their influence on the expression of IDD-associated autoantibodies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies in several Caucasian groups: 191 normal controls, 378 IDD patients, and 357 non-diabetic relatives of which 250 had no aAb, 107 had at least on aAb (79 ICA+, 31 GAD65 + and 49 IAA+), and 23 had both ICA+ and IAA+. We found that the frequencies of DR3/4 or DQB1*0201/0302 heterozygotes were significantly higher in aAb+ relatives compared to aAb- relatives. The frequencies of DR4/4 or DR4/X (X=non 3 or 4) and DQB1*0302/X (X=0201 or 0302) in aAb+ relatives were not different from the aAb relatives (which were enriched for these haplotypes), but were significantly higher than normal controls. The frequencies of DR3/X or DQB1*0201/X were decreased in both aAb+ relatives and IDD patients. Interestingly, the dominant IDD-protective DQB1*0602 allele allowed the development of individual aAbs (10% of ICA+ and 8% IAA+ relatives had the allele), but was not observed in any high risk double aAb+, or GAD65Ab+ relatives. The latter finding was similar to that in our patients with IDD, in that only two of them (0.5%) had a DQB1*0602 allele. In conclusion, HLA-encoded susceptibilities to disease-relevant autoantibody production and IDD are concordant with the susceptibility alleles, but discordant for the protective DQB1*0602. Thus HLA genotyping for DQB1*0602 would impact on the selection of aAb+ relatives for disease prevention trials.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalJournal of Autoimmunity
Volume7
Issue number6
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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HLA-DQ Antigens
HLA-DR Antigens
Autoantibodies
Genotype
Insulin
Alleles
HLA-DQB1 antigen
HLA-DRB1 Chains
MHC Class II Genes
Disease Susceptibility
Heterozygote
Gene Frequency
Haplotypes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them. / Huang, Wei; She, Jin-Xiong; Muir, Andrew; Laskowska, Danuta; Zorovich, Barbara; Schatz, Desmond; Maclaren, Noel K.

In: Journal of Autoimmunity, Vol. 7, No. 6, 01.01.1994, p. 889-897.

Research output: Contribution to journalArticle

Huang, Wei ; She, Jin-Xiong ; Muir, Andrew ; Laskowska, Danuta ; Zorovich, Barbara ; Schatz, Desmond ; Maclaren, Noel K. / High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them. In: Journal of Autoimmunity. 1994 ; Vol. 7, No. 6. pp. 889-897.
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abstract = "Although HLA class II genes are important in insulin-dependent diabetes (IDD), their influence on the expression of IDD-associated autoantibodies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies in several Caucasian groups: 191 normal controls, 378 IDD patients, and 357 non-diabetic relatives of which 250 had no aAb, 107 had at least on aAb (79 ICA+, 31 GAD65 + and 49 IAA+), and 23 had both ICA+ and IAA+. We found that the frequencies of DR3/4 or DQB1*0201/0302 heterozygotes were significantly higher in aAb+ relatives compared to aAb- relatives. The frequencies of DR4/4 or DR4/X (X=non 3 or 4) and DQB1*0302/X (X=0201 or 0302) in aAb+ relatives were not different from the aAb− relatives (which were enriched for these haplotypes), but were significantly higher than normal controls. The frequencies of DR3/X or DQB1*0201/X were decreased in both aAb+ relatives and IDD patients. Interestingly, the dominant IDD-protective DQB1*0602 allele allowed the development of individual aAbs (10{\%} of ICA+ and 8{\%} IAA+ relatives had the allele), but was not observed in any high risk double aAb+, or GAD65Ab+ relatives. The latter finding was similar to that in our patients with IDD, in that only two of them (0.5{\%}) had a DQB1*0602 allele. In conclusion, HLA-encoded susceptibilities to disease-relevant autoantibody production and IDD are concordant with the susceptibility alleles, but discordant for the protective DQB1*0602. Thus HLA genotyping for DQB1*0602 would impact on the selection of aAb+ relatives for disease prevention trials.",
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T1 - High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them

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AU - She, Jin-Xiong

AU - Muir, Andrew

AU - Laskowska, Danuta

AU - Zorovich, Barbara

AU - Schatz, Desmond

AU - Maclaren, Noel K.

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AB - Although HLA class II genes are important in insulin-dependent diabetes (IDD), their influence on the expression of IDD-associated autoantibodies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies in several Caucasian groups: 191 normal controls, 378 IDD patients, and 357 non-diabetic relatives of which 250 had no aAb, 107 had at least on aAb (79 ICA+, 31 GAD65 + and 49 IAA+), and 23 had both ICA+ and IAA+. We found that the frequencies of DR3/4 or DQB1*0201/0302 heterozygotes were significantly higher in aAb+ relatives compared to aAb- relatives. The frequencies of DR4/4 or DR4/X (X=non 3 or 4) and DQB1*0302/X (X=0201 or 0302) in aAb+ relatives were not different from the aAb− relatives (which were enriched for these haplotypes), but were significantly higher than normal controls. The frequencies of DR3/X or DQB1*0201/X were decreased in both aAb+ relatives and IDD patients. Interestingly, the dominant IDD-protective DQB1*0602 allele allowed the development of individual aAbs (10% of ICA+ and 8% IAA+ relatives had the allele), but was not observed in any high risk double aAb+, or GAD65Ab+ relatives. The latter finding was similar to that in our patients with IDD, in that only two of them (0.5%) had a DQB1*0602 allele. In conclusion, HLA-encoded susceptibilities to disease-relevant autoantibody production and IDD are concordant with the susceptibility alleles, but discordant for the protective DQB1*0602. Thus HLA genotyping for DQB1*0602 would impact on the selection of aAb+ relatives for disease prevention trials.

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