The Ocular Muscle Cell Is a Target of the Immune System in Endocrine Ophthalmopathy

Abstract

The exact pathogenic mechanism of thyroid-associated ophthalmopathy (TAO) remains unclear, and extensive studies on this disorder have resulted in often conflicting data. Well-known technical difficulties including the limited access to orbital tissues from patients with active and early disease, lack of an animal model and poor reproducibility of some of the immunological techniques used are in part responsible for this confusing situation. Despite this there is considerable evidence for eye muscle (EM) tissue involvement in the autoimmune reactions of TAO. Although the primary EM antigen(s) recognized by immunocompetent cells and autoantibodies has not been definitely identified, some good candidates, among them a membrane antigen of 64 kD which is also expressed in the thyroid, have been partially characterized. While it is unclear which component of the autoimmune reaction against EM – humoral or cell mediated – plays the more important role, autoantibodies seem to be responsible at least in part for the clinical features of the eye disorder. On the other hand, the orbital connective tissue (OCT) cells, especially the fibroblasts surrounding the EM fibers, seem to be extremely sensitive to stimulation by cytokines and other soluble proteins and immunoglobulins released in the course of an immune reaction in the muscle cells. Fibroblasts secrete large amounts of glycosaminoglycans and also participate in maintaining the autoimmune reaction. It seems likely that the EM is the main and primary target of the orbital autoimmune process whereas inflammation of the OCT is probably secondary.

Peripheral Blood Lymphocyte Transformation to G2s in Patients with Autoimmune Thyroid Disease with and without Ophthalmopathy

“…[4,5] In an earlier study, T lymphocytes obtained from orbital tissue and peripheral blood of TAO patients were activated by protein fractions from the eye muscles and OCT. [6] We have postulated that a shared auto-antigen in the orbit and thyroid gland, such as G2s or the TSH receptor (TSHR), is the target(s) of the cellular and humoral immune reactions in TAO. [3,7,8] Of the several eye muscle antigens that have been identified as targets for autoantibodies in TAO (reviewed in Ref. [3]), the novel protein G2s, which is strongly expressed in eye muscles, thyroid and other skeletal muscles, [9] the "55 kDa eye muscle membrane protein" identified in our earlier studies (reviewed in Ref.…”

Neutrophils from Brazilian patients with Graves' disease: some biochemical and functional aspects

“…7 TSH receptor antibodies are able to recognize ocular muscles and orbital tissue structures, 8,9 immunocomplexes (IC) and complement proteins (C) are also present in these inflamed tissues. 10 Infiltration of inflammatory cells and lymphocytes that liberate chemical mediators, which in turn will induce fibroblast proliferation and accumulation of hydrophilic glycosaminoglycans (GAG) is characteristic.…”

Role of Cytokines in the Pathogenesis of Thyroid-Associated Ophthalmopathy

“…There is some damage to EM fibers, although it is controversial (15,16). Most of the infiltrated lymphocytes are T cells and macrophages.…”

“…Both CD4 1 T cells and CD8 1 T cells were present and CD45RO 1 T cells (memory T cells) are predominant in early, active TAO specimens. CD45RA 1 T cells are few (5,15,16). In contrast, in patients who are in the late, inactive stage of the disease or have received irradiation or immunosuppressive therapy before surgery, there is some fibrosis, but the lymphocytic infiltration disappear and the EM cells appear to be less damaged or intact (5,16).…”