Occupational and environmental causes of sarcoidosis: clarifying epidemiology, improving in vitro detection, and development of an animal model

Sarcoidosis is a systemic disease of unknown etiology. It is a moderately frequent disease (annual incidence of 1 to 35 per 100,000 adults) characterized by the development of granulomas, mainly in the lung and lymph nodes. Although the etiology is unknown, there are strong indications that environmental exposures, mainly in the workplace, may be involved in causing or triggering the disease. Thus, sensitization to beryllium may lead to a disease (chronic beryllium disease or berylliosis) that is almost identical to sarcoidosis, and a higher risk of sarcoidosis has also been associated with exposures to various other metals (zirconium, aluminium,…) and mineral agents (silica, silicates, …). We, and others, have previously shown that the ex vivo lymphocyte proliferation test (LPT), which is considered the golden standard for diagnosing chronic beryllium disease, can be used to demonstrate sensitization to other metallic agents. We have preliminary evidence that the LPT can also be positive when lymphocytes are exposed to nanoparticles of silica, an original finding that has not been previously reported by others.In this multi-disciplinary project we intend,- to optimize the lymphocyte proliferation tests for use with nanosilica and relevant metals and metal oxides- to verify the contribution of the optimized LPT for the etiological diagnosis of sarcoidosis- to verify the use of the LPT as an early biomarker of effects of silica and other metallic agents in workers.- to develop a mouse model for sarcoidosis

Keywords:Sarcoidosis, Silica, Occupational lung disease, Lymphocyte Proliferation Test, Metal exposure, Mouse model, Epidemiological research, Translational research, Multidisciplinary research

Disciplines:Microbiology, Systems biology, Laboratory medicine, Other chemical sciences, Nutrition and dietetics, Agricultural animal production, Food sciences and (bio)technology, Public health care, Public health sciences, Public health services, Social medical sciences