SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (SICAM-1) IN SERA OF PATIENTS WITH GRAVES OPHTHALMOPATHY AND THYROID-DISEASES

Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important rol e in a variety of inflammatory and immunemediated mechanisms, is stron gly expressed in retroocular connective tissue from patients with Grav es' ophthalmopathy (GO) and involved in lymphocyte attachment to cultu red retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Her e, we report the detection and functional activity of a soluble form o f the ICAM-1 molecule (sICAM-1) in sera from patients with GO and othe r thyroid diseases. Serum concentrations for sICAM-1 were determined u sing a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentr ations (all P < 0.000 1). In patients with Graves' disease (GD) withou t clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM -1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 s erum levels in patients with non-autoimmune hyperthyroidism due to a t oxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucoco rticoid therapy in nine patients who responded to this form of treatme nt with a decrease in periorbital inflammation. In contrast, sICAM-1 s erum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mo nonuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retrooc ular fibroblasts in a dose-dependent manner, up to a maximal stimulati on of approximately 5-5-fold (P < 0-001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedl y elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 m ay play a role in the ongoing immune process within the connective tis sue in GO.