IMMUNOGENETICS OF GRAVES' OPHTHALMOPATHY

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Abstract
We have performed an immunogenetic analysis of 53 patients with severe Graves'' ophthalmopathy, 51 patients with Graves'' disease but little or no clinically apparent eye disease, and 90 controls. The distribution of restriction fragment length polymorphisms was analysed in the three groups, using probes for the HLA-DQ.alpha. and DR.beta. regions, the T-cell receptor C.alpha., V.alpha., C.beta. and J.gamma. genes and the immunoglobulin gene switch regions, S.alpha. and S.mu.. There was no abnormal distribution of these polymorphisms in either group of Graves'' patients, or differences between the Graves'' patients with or without eye disease. It was possible to assign HLA-DR types in most patients using the polymorphisms found after probing with DQ.alpha. and DR.beta.; there was no abnormal distribution of DR types in the two Graves'' groups. These results fail to confirm the reported associations between ophthalmopathy and HLA-DR3 and between Graves'' disease and the T-cell receptor C.beta. polymorphism; they also argue against a strong influence of Gm allotypes in Graves'' disease since these genes are in linkage disequilibrium with the S.alpha. polymorphisms. The association of Graves'' disease with HLA-DR3, defined hitherto using serological reagents, may be less strong than previously described.