Crystalline silica (quartz) contributes to development of several systemic autoimmune diseases, including RA, systemic sclerosis (SSc), SLE and anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. Solvents contribute to development SSc. Smoking contributes to development of anti-citrullinated protein antibody (ACPA)-positive and anti-rheumatoid factor. (RF)-positive RA (with an interaction with the shared eptiope genetic susceptibility factor). The gene discussed is PRTN3; the disease is systemic sclerosis.