Study Of ICAM-1 And Its Soluble Form In Pathogenesis Of Thyroid Associated Ophthalmopathy

Thyroid associated ophthalmopathy(TAO) is an autoimmune disease, of which incidence is the highest in adult orbital disease, about 20%, prominently involving both the extroocular muscles, the retroorbital fat/connective tissue and the lacrimal glands, so its clinical manifestations are impairment of eye movement, proptosis, lacrimation(stimulated by inflammation) or dry eye(when lacrimal glands involved seriously).Intercellular adhesion molecule-1 (1CAM- l),a member of the immuneglubulin supergene family, functions as a ligand for the lymphocyte function associated antigen-1 (LFA-1). ICAM-1 plays an important role in a variety of inflammatory and immune-mediated mechanisms, including lymphocyte recruitment and targeting, antigen presentation and recognition, and lymphocyte cytotoxicity. Now, some theses reported the localization and intense enhanced in situ of ICAM-1 in orbital connective tissues derived from patients with TAO. It is suggested that retroorbital fibroblasts are both target cells and effector cells in the ongoing immune process in orbit in TAO. However, pathology and pathogenesis of swelling lacrimal glands in TAO has not been reported.In addition to surface ICAM-1 expression, increased levels of circulating form of this molecule (sICAM-1) have been found in sera of TAO patients with or without Graves disease. But, we don't know weather serum sICAM-1 levels could reflect the degree of orbital inflammatory activity. Further, we want to clarify the correlation between sICAM-1 levels and thyroid hormone levels in TAO.The aim of this thesis is to try to answer these questions.Results:1. By detecting 15 pathologic slices of swelling lacrimal glands in TAO, we found the main changes were lymphocytic infiltration and edema, not proliferation offobroblasts.2.Using immunohistochemical technology, we determined vascular endotheliums and lymphocytes were strongly positive for ICAM-1 in swelling lacrimal glands in TAO. Specially, lacrimal gland acinar epitheliums of TAO more strongly expressed ICAM-1 (p<0.01)and HLA-DR ( p<0.01)than controls.3.Measured by a sandwich ELISA method, sICAM-1 levels signifcantly elevated in all groups of Graves disease patients with (1474.9+179.77ng/ml, p<0.01) or without TAO (873.3 ?134.58ng/ml, p<0.01) compared with controls (426.8 ?77.19ng/ml). And, Graves disease patients with TAO showed a significant increase of sICAM-1 levels compared those without TAO (p<0.01). Further, sICAM-1 levels from the group of activity TAO were significantly higher than those from non-activity TAO (1127.1 ?190.01 vs 638.3 ?6.44ng/ml, p<0.01).4.Semm T3 (2.3+0.64 vs 2.1?.71 nmol/1, p>0.05) and T4 (112.4?9.32 vsl 19.2+22.35 nmol/1, p>0.05) levels of the group of activity TAO werenot significantly different from those of the group of non-activty TAO. There weren't correlation between sICAM-1 levels and T3 (r=0.060, p>0.05), T4 (r=0.231, p>0.05).Conclusion:l.In swelling lacrimal glands of TAO, ICAM-1 most likely plays important roles of autoimmune attacking. Acinar epitheliums may be the target cells in swelling lacrimal glands of TAO.2. Elevated expression in situ of ICAM-1 in orbital tissues is the important source of serum sICAM-1 in TAO. It may play an important role in the ongoing immune process. Moreover, sICAM-1 levels are positively correlated to the clinical activity score of TAO suggesting that it may be considered as a marker reflecting the degree of orbital inflammatory activity.3.No correlation were detected between serum sICAM-1 levels and T3, T4 levels.