Detection, epitope‐mapping and function of anti‐Fas autoantibody in patients with silicosis

Abstract

Summary 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.

Dysregulation of the immune system caused by silica and asbestos

“…as topoisomerase I and desmoglein (Ueki A et al, , 2002Takata-Tomokuni et al, 2005). Anti-Fas autoantibody detected in SPs was functionally 2.…”

Reduced Function of CD4+25+ Regulatory T Cell Fraction in Silicosis Patients

“…In addition, a small number of silicosis patients had seemed to develop immunological diseases without presenting respiratory disorders after exposure to silica compounds (7). In addition, many autoantibodies were found in these patients (17)(18)(19)(20)(21).…”

Neurogenic Chronic Intestinal Pseudo-Obstruction: Antineuronal Antibody-Mediated Activation of Autophagy Via Fas

“…This observation supports the presence of naturally occurring agonist anti-Fas autoantibodies in the sera of healthy individuals. 41 We hypothesize that under circumstances of chronic inflammation or active autoimmune disorders the titer of agonist vs. antagonist antiFas autoantibodies favors production of the former.…”