Huang W, She J X, Muir A, Laskowska D, Zorovich B, Schatz D, Maclaren N K
Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.
J Autoimmun. 1994 Dec;7(6):889-97. doi: 10.1006/jaut.1994.1073.
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 one aAb (79 ICA+, 31 GAD65+ and 49 IAA+), and 23 had both ICA+ and IAA+. We found that the frequencies of DR3/4 or DQB10201/0302 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 DQB10302/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 DQB10201/X were decreased in both aAb+ relatives and IDD patients. Interestingly, the dominant IDD-protective DQB10602 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 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 DQB10602. Thus HLA genotyping for DQB1*0602 would impact on the selection of aAb+ relatives for disease prevention trials.
尽管人类白细胞抗原（HLA）Ⅱ类基因在胰岛素依赖型糖尿病（IDD）中很重要，但其对IDD相关自身抗体（aAb）表达的影响尚不清楚。我们比较了几个白种人群体中HLA - DRB1和DQB1基因频率：191名正常对照者、378名IDD患者以及357名非糖尿病亲属，其中250名无自身抗体，107名至少有一种自身抗体（79名胰岛细胞抗体阳性[ICA +]、31名谷氨酸脱羧酶65抗体阳性[GAD65 +]和49名胰岛素自身抗体阳性[IAA +]），23名同时有ICA +和IAA +。我们发现，与无自身抗体的亲属相比，有自身抗体的亲属中DR3/4或DQB10201/0302杂合子的频率显著更高。有自身抗体的亲属中DR4/4或DR4/X（X = 非3或4）以及DQB10302/X（X = 0201或0302）的频率与无自身抗体的亲属（这些单倍型在他们中富集）没有差异，但显著高于正常对照者。有自身抗体的亲属和IDD患者中DR3/X或DQB10201/X的频率均降低。有趣的是，主要的IDD保护性等位基因DQB10602允许个体自身抗体的产生（10%的ICA +亲属和8%的IAA +亲属携带该等位基因），但在任何高风险的双重自身抗体阳性或GAD65抗体阳性亲属中均未观察到。后一发现与我们的IDD患者相似，即他们中只有两人（0.5%）携带DQB10602等位基因。总之，HLA编码的与疾病相关的自身抗体产生和IDD的易感性与易感等位基因一致，但与保护性的DQB10602不一致。因此，对DQB1*0602进行HLA基因分型将影响为疾病预防试验选择有自身抗体的亲属。
