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 Scopus citations

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 - Dec 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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