Genetic heterogeneity in thyrotoxicosis patients with and without endocrine ophthalmopathy.

HLA antigens and humoral antithyroid immunity have been studied in 97 thyrotoxic patients [48 without and 49 with endocrine ophthalmopathy (EOP)]. A statistical significant increase of HLA-B8 frequency could be observed only in the thyrotoxic patients with EOP, whereas in patients without EOP B8 frequency was similar as to the one in the controls. The C locus antigen Cw3 was significantly different between both groups of patients: increased in those with EOP and statistically significantly decreased in those without EOP. Thyroid microsomal antibodies were found to be associated with HLA-B8 positivity and were noted with highest incidence in B8 positive EOP patients. No such association was observed for thyroglobulin antibodies. These data show a genetic heterogeneity in thyrotoxicosis patients with and without EOP. HLA-Cw3 positivity represents and increased risk to develop EOP in thyrotoxicosis, as frequency of this antigen was significantly decreased in thyrotoxicosis patients without any signs of EOP. The increased frequency for microsomal antibodies in thyrotoxic patients with EOP, especially in B8 positives underlines the genetically influenced autoimmune reactivity in that disorder.