Related Experiment Videos
Serum concentration of soluble Fas in patients with autoimmune thyroid diseases
Y Shimaoka1, Y Hidaka, M Okumura
1Department of Laboratory Medicine, Osaka University Medical School, Suita, Japan.
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.
Insights
Soluble Fas (sFas) levels differ in autoimmune thyroid diseases, increasing in Graves' disease and decreasing in Hashimoto's thyroiditis. These changes may impact thyroid cell apoptosis and antibody production.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- The Fas system regulates apoptosis, crucial for immune homeostasis.
- Dysregulation of Fas signaling is implicated in autoimmune diseases.
- Soluble Fas (sFas), a product of alternative splicing, inhibits Fas-mediated apoptosis.
Purpose of the Study:
- To investigate serum levels of soluble Fas (sFas) in patients with autoimmune thyroid diseases.
- To correlate sFas levels with disease activity and thyroid hormone status.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify serum sFas levels.
- Patients included those with Graves' disease, Hashimoto's thyroiditis, silent thyroiditis, and healthy controls.
- Statistical analysis was performed to compare groups and assess correlations.
Main Results:
- Serum sFas levels were elevated in active Graves' disease but decreased in Graves' disease remission and euthyroid Hashimoto's thyroiditis compared to controls.
- sFas levels did not directly correlate with thyroid hormone levels but showed a correlation with free thyroxine.
- sFas levels correlated significantly with TSH receptor antibody activity in Graves' disease.
Conclusions:
- Altered sFas levels in autoimmune thyroid diseases suggest differential Fas pathway regulation.
- Increased sFas in Graves' disease may protect thyroid cells and autoreactive B cells from apoptosis, potentially promoting disease.
- Decreased sFas in Hashimoto's thyroiditis may enhance thyroid cell apoptosis, contributing to tissue destruction.