In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than am ong controls (χ2 = 4.71, p<0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patients clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster. Although Gm interacted with HLA in enhancing the susceptibilitty Graves' disease (odds ratio DR3+ fb+ is 8.49, DR3+ fb- is 5.08, and DR3- fb+ is 1.42), this phenotype was distributed equally between the two clusters (48% in C1 and 58% in C2). We conclude that the use of HLA together with relatively few clinical characteristics results in the segregation of a severe and mild for of Graves' disease, and defines which individuals will respond to treatment with antithyroid drugs.
|Number of pages||9|
|Journal||Molecular Biology and Medicine|
|Publication status||Published - Nov 12 1986|
ASJC Scopus subject areas
- Molecular Biology