Increased serum soluble Fas in patients with Graves' disease

We addressed the role of soluble Fas (sFas), which suppresses Fas-mediated apoptosis, in the pathogenesis of Graves' disease (GD). The serum concentra tion of sFas was measured by enzyme-linked immunosorbent assay and the expr ession of sFas mRNA in thyroid tissues by reverse transcriptase-polymerase chain reaction. The serum concentration of sFas was significantly increased in untreated GD (mean +/- SD: 1.57 +/- 0.48 ng/mL) compared to age-matched control subjects (0.77 +/- 0.46 ng/mL). The serum sFas level tended to dec rease after the medication of antithyroid drugs for 6 to 8 weeks and was si gnificantly decreased in patients who were euthyroid for more than 3 years (0.98 +/- 0.23 ng/mL), compared to that in untreated GD. The concentration of serum sFas was significantly correlated with anti-thyrotropin (TSH) rece ptor antibody titers, but not with the other clinical parameters (free trii odothyronine [FT3], free thyroxine [FT4], TSH, antithyroglobulin antibody t iter, antimicrosomal antibody titer, or I-123 uptake). The sFas mRNA was de tected in thyroid tissue, cultured thyrocytes, and intrathyroidal lymphocyt es. sFas was detected in supernatant of cultured thyrocytes from patients w ith GD. Its production by thyrocytes was induced by culture with interleuki n-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The prese nt study confirms serum sFas increases in GD and provides evidence of local production of sFas by thyrocytes and its regulation by cytokines. These da ta suggest that sFas may play a role in the pathogenesis of GD.