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.

The role of Fas-mediated apoptosis in thyroid disease

“…They confirmed that serum sFas increases in GD and provided evidence of local production of sFas by thyrocytes and its regulation by cytokines. These studies suggest that sFas, by interfering with the Fas±FasL interaction, may also play a role in the pathogenesis of GD (38,39).…”

“…The serum levels of sFas have recently been measured in patients with autoimmune thyroid diseases (38). In contrast to normal controls, sFas was increased in thyrotoxic patients with GD, but reduced in patients with GD in remission.…”

“…The increased sFas may block this process and B cells escaping that deletion may be responsible for the production of TSH receptor antibody in GD (38). Apparently, the soluble form of Fas seems to be involved in the pathogenesis of GD, but further studies are needed to determine either the pathogenic or the protective role of sFas in this disease.…”

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

“…Local immunosuppressive regulatory cytokines (TGF-β and IL-10) may be involved in the maintenance of tolerance and prevention of AITD [18,19] . A decreased apoptosis of activated T cells, like in defects of interaction of Fas (CD95) and Fas ligand (Fas-L), has been studied in AITD [20] . The proportion of intrathyroidal natural killer T cell subset has been found lower in GD than in the peripheral blood of the same patients and of controls, contributing to the incomplete regulation of autoreactive T cells [13] .…”

Soluble fas antigen in serum of cancer patients

“…Elevated blood concentration of sFas was observed in some autoimmune disease: systemic lupus erythematosus [15], cutaneous tuberculosis [4], Graves' disease [13], as well as in patients with myocarditis, heart failure [12], T and B cell leukemia [8], and hepatocellular carcinoma [61.…”