W. Huang et al., HIGH-RISK HLA-DR DQ GENOTYPES FOR IDD CONFER SUSCEPTIBILITY TO AUTOANTIBODIES BUT DQB1-ASTERISK-0602 DOES NOT PREVENT THEM/, Journal of autoimmunity, 7(6), 1994, pp. 889-897
Although HLA class II genes are important in insulin-dependent diabete
s (IDD), their influence on the expression of IDD-associated autoantib
odies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies
in several Caucasian groups: 191 normal controls, 378 IDD patients, a
nd 357 non-diabetic relatives of which 250 had no aAb, 107 had at leas
t one aAb (79 ICA(+), 31GAD(65)(+) and 49 IAA(+)), and 23 had both ICA
(+) and IAA(+). We found that the frequencies of DR3/4 or DQB10201/03
02 heterozygotes were significantly higher in aAb(+) relatives compare
d to aAb(-) relatives. The frequencies of DR4/4 or DR4/X (X=non 3 or 4
) and DQB10302/X (X=0201 or 0302) in aAb(+) relatives were not differ
ent from the aAb(-) relatives (which were enriched for these haplotype
s), but were significantly higher than normal controls. The frequencie
s of DR3/X or DQB10201/X were decreased in both aAb(+) relatives and
IDD patients. Interestingly, the dominant IDD-protective DQB10602 all
ele allowed the development of individual aAbs (10% of ICA(+) and 8% I
AA(+) relatives had the allele), but was not observed in any high risk
double aAb(+), or GAD(65)Ab(+) relatives. The latter finding was simi
lar to that in our patients with IDD, in that only two of them (0.5%)
had a DQB10602 allele. In conclusion, HLA-encoded susceptibilities to
disease-relevant autoantibody production and IDD are concordant with
the susceptibility alleles, but discordant for the protective DQB1060
2. Thus HLA genotyping for DQB10602 would impact on the selection of
aAb(+) relatives for disease prevention trials.