title: Serum concentration of soluble Fas in patients with autoimmune thyroid diseases.
abstract: Fas is an apoptosis-signaling receptor molecule found on the surface of a number of cell types. Malfunction of the Fas system accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction. Soluble Fas (sFas) molecule lacks the transmembrane domain due to alternative splicing and blocks Fas-mediated apoptosis. This study investigated serum levels of sFas in autoimmune thyroid diseases. Serum levels of sFas were determined by enzyme-linked immunosorbent assay in 46 patients with Graves' disease, 32 patients with Hashimoto's thyroiditis, 14 patients with silent thyroiditis, and 24 normal controls. Compared with normal subjects (1.43+/-0.37 ng/mL), sFas was increased in thyrotoxic patients with Graves' disease (1.89+/-0.47 ng/mL, p < 0.001), and was decreased in patients with Graves' disease in remission (1.02+/-0.41 ng/mL, p < 0.001) and in euthyroid patients with Hashimoto's thyroiditis (0.97+/-0.25 ng/mL, p < 0.0001), but was normal in hypothyroid patients with Hashimoto's thyroiditis and in thyrotoxic patients with silent thyroiditis. Thus, changes in serum levels of sFas could not be explained by changes in serum thyroid hormones, although sFas concentration correlated with free thyroxine (r = 0.692, p < 0.0001). Also, the levels of sFas significantly correlated with the activities of TSH receptor antibody in Graves' disease (r = 0.671, p < 0.0001). Increased sFas in Graves' disease suggests increased expression of alternatively spliced Fas mRNA variant that produces sFas protein and decreased of cell surface expression of Fas, and may induce thyroid cell growth and production of TSH receptor antibody by protecting against apoptosis of thyroid cells and autoreactive B cells. Decreased sFas in Hashimoto's thyroiditis suggests decreased Fas mRNA variant and increased full-length Fas mRNA and membrane Fas, and may induce destruction of thyroid cells by promoting apoptosis of thyroid cells.
authors.affiliation: Department of Laboratory Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Hidaka
authors.forename: M
authors.initials: M
authors.lastname: Okumura
authors.forename: K
authors.initials: K
authors.lastname: Takeoka
authors.forename: H
authors.initials: H
authors.lastname: Tada
authors.forename: N
authors.initials: N
authors.lastname: Amino
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D011989:Receptors, Thyrotropin / Q000276:immunology; D012995:Solubility; D013959:Thyroid Diseases / Q000097:blood* / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood; D019014:fas Receptor / Q000097:blood*
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D019014:fas Receptor