title: Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism.
abstract: Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.
authors.affiliation: Graduate Institute of Physiology, and the Division of Endocrinology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Wang
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Zhong
authors.forename: Tien-Chun
authors.initials: TC
authors.lastname: Chang
authors.forename: Yuan-Feen
authors.initials: YF
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D053222:Fas Ligand Protein; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000276:immunology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011989:Receptors, Thyrotropin / Q000097:blood; D019014:fas Receptor / Q000097:blood
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018828:Immunoglobulins, Thyroid-Stimulating; D008562:Membrane Glycoproteins; D011989:Receptors, Thyrotropin; D019014:fas Receptor; C094372:thyrotropin-binding inhibitory immunoglobulin