Human orbital tissue and thyroid membranes express a 64 kDa protein which is recognized by autoantibodies in the serum of patients with thyroid‐associated ophthalmopathy

Abstract

A 64 kDa protein has been identified in the membrane fraction of human eye muscle, orbital connective tissue and thyroid, by testing sera of patients with thyroid-associated ophthalmopathy in SDS-polyacryltide gel electrophoresis and Western blotting. Antibodies to this membrane antigen seem characteristic of the early stage of ophthahnopathy. In the thyroid this newly recognixed protein seems different from previously known membrane antigens. A thyroid antibody reactive with a 64 kDa membrane antigen in eye muscle could explain the very frequent association of ophthalmopathy with autoimmune thyroid disease.

A Possible Common Cell Surface Autoantigen in Islet .BETA.-Cells and Thyroid Follicular Cells in Patients with Non-lnsulin Dependent Diabetes Mellitus and Chronic Thyroiditis.

“…In addition, other endocrine cells, such as pituitary cells and adrenal chromaffin cells, are known to have GAD, but are not always confined to GAD65 [37]. Furthermore, it was reported that autoantibodies to a 64 kDa protein isolated from the human thyroid and retroorbital tissue were identified in the sera of patients with thyroid-associated ophthalmopathy [38] and the same autoantibodies cross-reacted with a 64 kDa antigen expressed on the surface of human pancreas cell membranes [39]. But it is not yet clear whether the thyroid 64 kDa protein is similar to the 64 kDa islet autoantigen (GAD65) [39].…”

Significance of Thyroid Stimulating Antibody and Long Term Follow Up in Patients with Euthyroid Graves' Disease.

“…Furthermore, Salvi [13] and Weetman [14] reported that patients with euthyroid Graves' disease show certain abnormalities in the thyroid.…”

Anti-Eye Muscle Antibodies and Hypothyroid Graves' Disease: A Case Report.

“…However, Ahmann et al [7] and Weightman et al [9] found that normal sera also bound to a 64kDa protein and argued against the pathological significance of this protein. Conversely, Salvi et al [6] reported that 50% of patients with TAO, but no normal subjects, have antibodies against a 64kDa protein.…”

“…The results suggest a relationship between these antibodies and ophthalmopathy in hypothyroid Graves' disease. In recent years, antibodies to a 64kDa protein in porcine eye muscle [7,9] and in human eye muscle [6,8] have been reported in TAO. However, Ahmann et al [7] and Weightman et al [9] found that normal sera also bound to a 64kDa protein and argued against the pathological significance of this protein.…”

“…To our knowledge, most patients with TAO have detectable serum anti-TSH receptor antibodies, even if they are associated with hypothyroidism [2], although a possible role of anti-TSH receptor antibodies in the development of ophthalmopathy has never been shown. Eye muscle antibodies as measured in enzyme linked immunosorbent assay [3,4], antibody-dependent cell-mediated cytotoxicity assay [5] and Western blotting [6][7][8][9], have been found in sera from patients with TAO, although their precise roles in the development of TAO are still unclear. In the present studies, we report a case of so-called "hypothyroid Graves' disease" [10] during lithium therapy.…”