👤 A Kromminga

Endocrine ophthalmopathy is a chronic eye disease, characterized by inflammation in parabulbar and retrobulbar space, occurring usually in Graves' thyrotoxicosis. Although the pathogenesis of the disease has not been clarified until now, it is accepted that this disease is of an autoimmune nature, where the targets of the autoimmune reaction are the antigens shared by thyroid and orbit-tissue. The autoantibodies against recombinant 1D protein are highly specific and sensitive for the diagnosis of endocrine orbitopathy. The aim of our study was to establish, whether the autoantibodies against 1D protein are found predominantly in patients with clinically expressed endocrine orbitopathy. We evaluated in 30 patients with clinically expressed endocrine orbitopathy the thickness of the three retrobulbar eye muscles, damaged by endocrine orbitopathy, determined the parameters of thyroid hormones and anti-TSH receptor autoantibodies. In all patients the detection of circulating autoantibodies against recombinant 1D protein was performed. Autoantibodies against recombinant 1D protein were found in all patients with clinically expressed endocrine orbitopathy. Immunoreactivity did not depend on the duration or severity of the eye disease, neither on patients' age. We did not find any correlation between the thickness of eye muscles and the titre of anti-TSH receptor autoantibodies, levels of ssTSH and free thyroxine and also any correlation between the thickness of eye muscles and the disease duration. Show less

Thyroid-associated ophthalmopathy (TAO) is a potentially severe autoimmune disease, in and around the orbit, usually accompanied by Graves' disease. It was the goal of this study to develop a serological indicator for TAO and to characterize its expression in human thyroid and eye muscle tissue. Thus, we have recloned the full-length 1D-complementary DNA and assessed its expression levels in 90 healthy and diseased human thyroids. Only Graves' patients suffering from TAO (n = 29) displayed a significant, 2.1-fold increase of 1D expression levels (P = 0.029), compared with normal controls (n = 9), as assessed using the Mann-Whitney U-test for paired, nonnormally distributed samples. In contrast, a decrease of 1D expression (to 40% of control normal values) was confined to thyroid autonomy (n = 19, P = 0.032). In all other diseased human thyroids, including Graves' thyroids from patients not suffering from clinically overt TAO (n = 9), 1D expression levels were not different from the healthy controls. 1D gene expression was demonstrated in both healthy (n = 10) and diseased (n = 10) eye muscle tissues. Furthermore, a recombinant protein derived from baculovirus-infected Sf9 insect cells was purified under both nondenaturing and denaturing conditions. While under nondenaturing conditions, the molecular mass of recombinant 1D was determined to be 85 kDa; denaturing isolation yielded the expected 64-kDa protein. Autoantibodies against denatured 1D protein were not detectable in sera of diseased or healthy subjects. Immunoreactivity against the 85-kDa, nondenatured protein, evaluated in a panel of 222 different human sera, showed that 82% of Graves' patients suffering from TAO had autoantibodies against recombinant 1D, whereas only 5% of the healthy controls were positive for antibodies against 1D. Taken together, our results demonstrate a high disease sensitivity and specificity of recombinant, nondenatured 1D, to distinguish Graves' disease with or without TAO from other forms of thyroid and/or eye disease. Prospective studies will have to show whether autoantibodies against 1D can also be used as a prognosticator of TAO. Show less