Autoimmunity in silica-exposed workers

Author(s)

Michelle Rocha Parise

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2012-01-26

Examining board members

Mary Luci de Souza Queiroz; Edson Antunes; Eduardo Mello De Capitani; Sara Teresinha Olalla Saad; Iracilda Zeppone Carlos; Claudia Bincoletto Trindade

• Advisor: Mary Luci de Souza Queiroz

Abstract

Crystalline silica, or quartz, is a mineral abundant in sand, rock and soil which chronic exposure is known to predispose to pulmonary lesions, fibroblasts proliferation and excessive collagen production in the lungs that leads to silicosis, a form of pulmonary fibrosis. Occupational exposure to crystalline silica dust has been examined as a possible risk factor with respect to several autoimmune diseases, such as rheumatoid arthritis, scleroderma and systemic lupus erythematosus. In this regard, silica has been known to have an adjuvant effect on immunocomplexes and immunoglobulins production in a nonspecific manner, thus reinforcing its relation with the appearance of autoimmunity. However, the relationship between silica exposure and the development of autoimmunity remains to be elucidated because the mechanisms underlying this association are unknown. It is unclear whether silicosis is only a marker for high-level silica dust exposure or whether it represents a pathologic process that may predispose some individuals to the development of autoimmune disease. Therefore, an accurate investigation of the autoimmunity indicators in silicotic individuals is required. Our results present evidences of alterations compatible with autoimmunity in silica-exposed individuals as compared to the control population by demonstrating an activation of humoral and cellular immune responses as well as functional alterations in T lymphocytes (LT). It was shown by the increased levels of antinuclear antibodies, rheumatoid factor and anti-endothelial cell antibodies, by the increased proliferative response of peripheral blood mononuclear cells, augmented levels of serum soluble Fas ligand, number of Natural Killer cells and alterations of IFN-_, TNF-_, IL-1_, IL-2, IL-6, IL-10 and TGF-_ cytokine levels as well as by functional LT alterations by thelower expression of CTLA-4 and PD-1 regulatory molecules. In addition, our study suggested a genetic influence in the expression of PD-1 receptor by its lower expression in the surface of T CD4+ cells in individuals carrying GG genotype in the study of PD1.3 polymorphism and also demonstrated that autoimmunity can occur before the clinical manifestations of silicosis (AU)