NATURE OF 64 KDA EYE MUSCLE AND THYROID MEMBRANE-PROTEINS AND THEIR SIGNIFICANCE IN THYROID-ASSOCIATED OPHTHALMOPATHY - AN HYPOTHESIS

Although a variety of eye muscle antigens are recognized by autoantibo dies in the serum from patients with thyroid associated ophthalmopathy (TAO) 64 kDa membrane proteins, which are also expressed in the thyro id, are most closely linked to the development of ophthalmopathy in pa tients with autoimmune thyroid disease. A cloned 64 kDa protein called 1D, which shares homology with tropomodulin, appears to be closely re lated to a 64 kDa eye muscle protein identified in immunoblotting and both may be members of a family of cytostructural proteins. The relati onship between 64 kDa proteins in eye muscle and thyroid, and its equi valent in somatic skeletal muscle, will only be understood when the va rious proteins are cloned from expression libraries, sequenced and the ir consensual and unique domains identified. Since these 64 kDa antige ns are expressed in both thyroid and eye muscle, a possible mechanism for the association of ophthalmopathy with autoimmune thyroid disease is immunological cross-reactivity by autoantibodies and sensitized T l ymphocytes. Autoantibodies reactive with 64 kDa eye muscle proteins ar e associated with ophthalmopathy in patients with autoimmune thyroid d isorders and predictive of the development of ophthalmopathy in patien ts with Graves' hyperthyroidism.