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 language | English (US) |
|---|---|
| Pages (from-to) | 889-897 |
| Number of pages | 9 |
| Journal | Journal of Autoimmunity |
| Volume | 7 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 1994 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them
AU - Huang, Wei
AU - She, Jin-Xiong
AU - Muir, Andrew
AU - Laskowska, Danuta
AU - Zorovich, Barbara
AU - Schatz, Desmond
AU - Maclaren, Noel K.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - 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.
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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U2 - 10.1006/jaut.1994.1073
DO - 10.1006/jaut.1994.1073
M3 - Article
VL - 7
SP - 889
EP - 897
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 6
ER -