HLA-DR1 is associated with vitiligo.

In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.

Immunogenetic and immunologic studies of differentiated thyroid cancer.

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell-mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/normal tissue interface. HLA-DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DR1 homozygotes were not at greater risk for thyroid cancer. The HLA-DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA-DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (less than 45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell-mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA-DR could not be related to cell-mediated immune response. Patients with papillary carcinoma with a good cell-mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell-mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.

Association of goitrous autoimmune thyroiditis with HLA-DR3 in eastern Hungary.

An association of HLA-DR5 and goitrous autoimmune thyroiditis has been reported elsewhere (Farid et al., 1981; Weissel et al., 1980). Recently, the disease was found to be associated with HLA-DR4 in Newfoundlanders (Farid & Thompson, 1986). In order to find out whether different HLA associations with the disease may be found in different ethnic groups, we have now typed 68 patients with autoimmune goitrous thyroiditis from Eastern Hungary for HLA-A, -B, -C, and -DR antigens; 66 of these patients were also typed for IgG heavy-chain markers (Gm). A significant increase in DR3 (OR = 3.30) and a non-significant increase in DR4 (OR = 1.67) were found in the patients when compared with controls. The Gm3 allele, g, interacted with DR3 to enhance the risk for goitrous autoimmune thyroiditis. Hashimoto's disease may show different associations in different ethnic groups, and indeed within the same ethnic group, when newly diagnosed patients are typed several years apart.

Genetic factors in Graves' ophthalmopathy.

We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA-DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P less than 0.0005). HLA-DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8- DR7- as reference, the odds ratios were 16.7 for B8+ DR7+, 8.7 for B8+ DR7- and 0.26 for B8- DR7+. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA-B8; the odds ratios were 20.9 for B8+ Gmfb homozygozity (fb+), 15.3 for B8+ fb- and 1.7 for B8- fb+ (B8- fb- = 1.00). We conclude that the genetic factors contributing to Graves' ophthalmopathy are different from those related to liability for Graves' hyperthyroidism.

Interaction of IgG heavy-chain allotypes (Gm) and HLA in conferring susceptibility to thyroid carcinoma.

We have recently reported an increase in HLA-DR1 in 52 patients with thyroid epithelial cancer from Eastern Hungary (Juhasz et al., 1986). We have now investigated the association of IgG heavy chain markers (Gm) in 50 patients with this disease and explored possible interaction between Gm and HLA in modifying the risk for thyroid cancer. No Gm phenotype showed significant increases in the patients compared to 168 local controls. When both Gm and HLA, however, were considered, a marked heterogeneity in risk was noted. The odds ratio for DR1+fb+ homozygotes was 37.5, for DR1+fb- individuals 6.0 and for DR1-fb+ individuals 2.6 (DR1-fb- = 1.0). Thus Gm and HLA interact to enhance greatly the risk of thyroid cancer.

The association of IgG heavy-chain allotypes (Gm) with Graves' disease in Hungary.

In an Eastern Hungarian population of patients, we sought to confirm an association with IgG heavy-chain allotypes (Gm) with Graves' disease. We found an increase in the phenotype fb (chi 2(1) = 4.7, p less than 0.05) among the patient group compared to controls. The influence of Ig-linked genes to Graves' disease susceptibility is, thus, dose-dependent. We found no interaction between fb homozygosity and HLA-DR3 positivity in Graves' disease susceptibility.