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Detection, epitope-mapping and function of anti-Fas autoantibody in patients with silicosis
Akiko Takata-Tomokuni1, Ayako Ueki, Mieko Shiwa
1Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan.
Abstract:
Dysregulation of apoptosis through the Fas-Fas ligand pathway is associated with the onset of autoimmune disease. Since autoantibodies directed against unknown antigens are present in the sera of these patients, sera samples were examined for the presence of autoantibodies directed against the Fas molecule. Using Western blotting and a ProteinChip analysis, autoantibodies against Fas were detected in patients with silicosis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and weakly detected in healthy individuals. Using epitope mapping employing 12-amino-acid polypeptides with the SPOTs system, a minimum of four epitopes and a maximum of 10 epitopes were found. Several amino acid residues involved in binding FasL, such as C66, R87, L90, E93 and H126, were presented within the epitopes. Serum containing a large amount of anti-Fas autoantibody from silicosis patients inhibited the growth of a Fas-expressing human cell line, but did not inhibit the growth of a low Fas-expresser nor a Fas-expresser in which the Fas gene had been silenced by small interference RNA. All epitopes in the intracellular region of Fas were located in the death domain. The possible roles of anti-Fas autoantibody detected in healthy volunteers and patients with silicosis or autoimmune diseases are discussed here.
Insights
Autoantibodies targeting the Fas molecule were found in patients with autoimmune diseases like SLE and SSc, and also in healthy individuals. These anti-Fas autoantibodies can inhibit cell growth, suggesting a role in disease pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Dysregulation of apoptosis via the Fas-Fas ligand pathway is implicated in autoimmune disease development.
- Patients with autoimmune diseases often exhibit autoantibodies against unknown antigens.
Purpose of the Study:
- To investigate the presence and characteristics of autoantibodies targeting the Fas molecule in patients with silicosis, systemic lupus erythematosus (SLE), and systemic sclerosis (SSc).
- To explore the functional impact of anti-Fas autoantibodies on Fas-expressing cells.
Main Methods:
- Western blotting and ProteinChip analysis were used to detect anti-Fas autoantibodies in patient sera.
- Epitope mapping with SPOTs system identified specific binding sites on the Fas molecule.
- Functional assays assessed the effect of anti-Fas autoantibodies on Fas-expressing cell lines.
Main Results:
- Autoantibodies against Fas were detected in patients with silicosis, SLE, and SSc, and also weakly in healthy individuals.
- Multiple epitopes, including residues critical for Fas ligand binding, were identified within the Fas molecule.
- High-titer anti-Fas autoantibodies from silicosis patients inhibited the growth of Fas-expressing cells.
Conclusions:
- The study identifies anti-Fas autoantibodies in various conditions, including autoimmune diseases and silicosis.
- The identified epitopes and functional inhibition suggest a role for anti-Fas autoantibodies in disease processes.
- Further investigation into the implications of anti-Fas autoantibodies in healthy individuals and disease states is warranted.