Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours

Abstract

SUMMARYSoluble Fas (sFas) is produced as translation products of alternative mRNA splicing, and antagonizes the membranous Fas molecule in Faspas ligand interactions. We investigated the serum sFas levels in 64 Japanese silicosis patients with no clinical symptoms of autoimmune diseases or malignant tumours, using ELISA for sFas. The serum sFas levels in the silicosis patients were significantly higher than those in healthy volunteers. Elevated serum sFas levels were also detected in patients with systemic lupus erythematosus but, unexpectedly, no difference was observed in sFas levels between progressive systemic sclerosis patients and healthy volunteers. On the other hand, there was no significant difference in the expression of Fas on peripheral blood lymphocytes between the patients with silicosis and agematched healthy volunteers. These observations provided the first evidence that serum sFas levels are elevated in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. It remains to be clarified whether patients with elevated sFas levels have a tendency to develop autoimmune diseases later, or whether some other distinct factor(s) is necessary to initiate the progression of autoimmune diseases.

Dysregulation of the immune system caused by silica and asbestos

“…than in healthy donors (HDs), although the level of serum soluble Fas ligand did not differ between SPs and HDs (Tomokuni et al, 1997(Tomokuni et al, , 1999. The mean fluorescent intensity (MFI) of membrane 4.…”

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

“…In addition, our previous results indicated that in silicosis patients, who did not manifest clinical signs and symptoms of autoimmune diseases, possessed the dysregulation of Fas-mediated apoptotic pathway in their lymphocytes and was disrupted (5)(6)(7)(8)(9)(10)(11). Therefore, autoimmunity may be affected at the cellular level in these patients.…”

Immunological Effects of Silica and Related Dysregulation of Autoimmunity

“…Anti-Fas autoantibody detected in SILs was functionally active and caused Fas-mediated apoptosis (takata- . The level of serum sFas was higher in SILs than healthy volunteers (HVs), although the level of serum soluble FasL did not differ between SILs and HVs (Tomokuni, 1997. The mean fluorescent intensity (MFI) of membrane Fas was lower with lymphocytes from SILs than those from HVs, although total numbers of Fas-positive lymphocytes (membrane Fas expression) did not differ between the two populations .…”