ANTIBODIES AGAINST STRIATED-MUSCLE, CONNECTIVE-TISSUE AND NUCLEAR ANTIGENS IN PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY - SHOULD GRAVES-DISEASE BE CONSIDERED A COLLAGEN DISORDER

The identity and subcellular localization of the principal extraocular muscle (EOM) antigens and prevalences of the corresponding serum auto antibodies in thyroid-associated ophthalmopathy (TAO) need to be clari fied. We have used porcine eye muscle tissue, which expresses all auto antigens identified in human tissue, as substrate in an indirect immun ofluorescence assay, Several different patterns of antibody binding to EOM tissue antigens were observed with sera from patients with TAO na mely, membrane, cytoplasmic, interstitial (endomysial) and nuclear. Ov erall, sera from 75% of patients with TAO contained one or more antibo dies reactive with EOM, compared to 32% of patients with Graves' hyper thyroidism, 38% with Hashimoto's thyroiditis, and 16% of normals. All sera which reacted with EOM membrane or cytoplasmic antigens also reac ted with the same antigen(s) in other skeletal muscle, but not in the other tissues tested. Sera from 31% of patients with TAO, but only 7% of those with Hashimoto's thyroiditis, and no patient with Graves' hyp erthyroidism without evident ophthalmopathy, contained antinuclear ant ibodies (ANA). The most common nuclear fluorescence pattern was the fi nely speckled type typically associated with anti-Sm or anti-RNP antib odies. Significant positive correlations in patients with TAO were fou nd between (i) EOM dysfunction and ANA (ii) eye disease of <1 yr durat ion and EOM membrane-reactive antibodies and (iii) eye disease of <1 y r duration and interstitial (endomysial) tissue-reactive antibodies. A lthough patients with Graves' disease do not usually exhibit other sig ns or immunologic features of a generalized collagen disorder, the fin ding of high prevalences of ANA and anti-striated muscle antibodies an d, less often, anti-connective tissue antibodies in patients with opht halmopathy, is consistent with it being a collagen-like disorder of th e striated muscle, connective tissue and the thyroid. The reason why t he inflammatory process is mainly limited to these tissues is unclear although cross reaction of ANA with tissue specific proteins or increa sed expression of muscle and connective tissue antigens in the orbit a nd skin, are possibilities. (C) 1997, Editrice Kurtis.