In situ studies of orbital tissue from patients with thyroid-associated ophthalmopathy

Abstract

Extensive studies have attempted to establish the nature of the orbital autoantigen(s) and the mechanism for the development of thyroid-associated ophthalmopathy (TAO). Histologic examination of the orbital tissues of patients with TAO has revealed lymphocytic infiltration in the extraocular eye muscles (EM) with an accumulation of glycosaminoglycans and some damage of EM fibers. CD4⁺, CD8⁺, CD45RO⁺ T cells and macrophages are predominant in EM during the active stage of TAO. Both Th1 and Th2 cytokines are present in EM tissues. The expression of HLA-DR on EM is seen in association with lymphocytic infiltration. The lack of the expression of B7 or B70 suggests that the aberrant expression of HLA-DR on EM may play a role in peripheral tolerance to EM antigens. Heat shock protein-70 is expressed in EM fibers from most of patients with TAO, suggesting that EM is the target of the autoimmune reaction. 1D, a candidate 64 kDa EM antigen, is present in both thyroid and EM. However, its clinical relevance has not yet been established. On the other hand, the presence of thyrotropin receptor (TSH-R) is demonstrated in human orbital tissues by RT-PCR and in cultured orbital fibroblasts by in situ hybridization. The failure to demonstrate the in vivo expression of TSH-R by immunohistochemistry, Northern blot or in situ hybridization suggests that the expression of TSH-R is low in the orbit. Further investigations are indicated to elucidate the factors which promote the expression of TSH-R in the orbit, and the nature of the primary autoantigen(s) in TAO.

Key Words:

• HLA-DR
• antigen
• immunohistochemistry
• lymphocyte phenotype
• in situ hybridization
• PCR
• heat shock proteins
• adhesion molecules