Autoantibodies in Silicosis Patients: Silica-Induced Dysregulation of Autoimmunity

Silica particles cause silicosis (SIL) and represent one of the most typical environmental and occupational substances that induce autoimmune disorders among the exposed population. Anti-nuclear antibody (ANA), anti-Sjögren’s-syndrome-related antigen A (SS-A), anti-centromere protein B (CENP)-B, and anti-scleroderma (Scl)-70 autoantibodies were examined in SIL and compared with those in healthy volunteers (HV) and patients with systemic sclerosis (SSc). Individuals with SIL were prone to autoimmune diseases and some autoantibodies seemed to be important as an estimation of this condition. Anti-Fas autoantibody found in SIL was functionally capable of inducing apoptosis in Fas-expressing cells, and this may cause a decrease of regulatory T cells (Tregs) expressing Fas in SIL. Moreover, responder T cells (Tresps) in SIL seemed to be activated chronically and protected from Fas-mediated apoptosis. Thus, an imbalance of Tresps (dominant) and Tregs (less) occurred in SIL. All of these causes of SIL are ready to further develop autoimmune diseases

Reduced Expression of the Survivin Gene in PBMC from Silicosis Patients

To explore the mechanism involved in immunological disorders associated with silicosis, the expression of IAP family genes in peripheral blood mononuclear cells from silicosis patients was examined. Relative gene expression was assayed using the multiplex RT-PCR for the XIAP and survivin genes. The correlation between those expression levels and various clinical parameters was then analyzed. The relative expression level of the survivin gene was reduced in silicosis patients as compared with that of healthy volunteers. The expression level of survivin positively correlated with PCO_2 values. These results support the existence of two populations of T lymphocytes in silicosis patients, one resistant to Fas-mediated apoptosis (a self-recognizing long-surviving fraction) and the other one sensitive to silica-induced apoptosis and repeatedly undergoing death and recruitment