Association of HLA antigen BW35 with severe Graves' ophthalmopathy

Human leukocyte antigens (HLA) in patients with Graves' disease were investigated according to the ophthalmic classification system of the American Thyroid Association. All prior HLA studies of Graves' disease have disregarded the patients' specific ophthalmic manifestations. Examination of 18 A and 34 B loci antigens disclosed an increased frequency (corrected P = 0.002, relative risk = 13.1) of HLA-BW35 in patients improving with oral corticosteroids who have severe extraocular muscle and orbital inflammation (class 4-5) when compared to a geographically and racially matched control population. No statistically significant associations were found when patients without ophthalmic manifestations or with other categories of Graves' ophthalmopathy were compared to controls. The association of severe Graves' ophthalmopathy with HLA-BW35 may provide immunologic evidence to explain both the unpredictable association of the orbital and thyroid disturbances of Graves' disease as well as the unpredictable response of the orbital inflammation to oral corticosteroids.