Serological and molecular studies of HLA in Sardinian patients with Graves' disease

HLA Class I and Class II antigens were studied in 103 unrelated Sardinian patients with Graves' disease (GD), 71 of whom had ophthalmopathy, and in 220 healthy controls. Molecular typing of the DQB1 allelic variants was carried out on 34 GD patients and 35 healthy controls, selected for the HLA-DR2-DQw1 phenotype. The results of the serological typing showed a positive association with the DR2 and the DQw1 antigens and a negative association with DR3 and DQw2 antigens. These associations were stronger in the GD patients with ophthalmopathy. The DQB1 molecular analysis in patients with the HLA-DR2-DQw1 phenotype revealed the presence of the DQB1*0502 allele in 91.1 per cent of the patients and in 82.2 per cent of the controls. In the Sardinian population GD seems to present a different HLA association than that observed in other Caucasian populations (DR3-Dw24). The DR2 and DQw1 positive associations may be explained by the high frequency of the DQB1*0502 allelic variant (37.7 per cent) which is rare in the other Caucasian populations. The absence of an association between DR3 and GD in Sardinia can be attributed to the very low frequency of the HLA-B8-DR3 (Dw24) haplotype. In fact, in the Sardinian population, DR3 is associated with the allelic variant Dw25 carried by the HLA-B18-DR3 haplotype.