Table 2.
Postulated mechanisms for xenobiotic-induced autoimmunity and autoimmune disease.
| Type of Exposure | Silica | Smoking | Solvents | Mercurya | Asbestos |
| Location | Lung | Lung | Lung/Skin | Lung/Skin/GI Tract | Lung |
| Inflammatory responses | IL-1α, IL-1β Inflammasome MyD88, IFN-γ, IL-17, type I IFN, IRF7 NETosis |
IL-1β Inflammasome IL-6, IL-8, TNF-α MyD88, NETosis |
ND | Endosomal TLRs IL-6, TNF-α, IFN-γ NETosis |
IL-1β Inflammasome |
| Self-Protein Modifications | Citrullination Carbonylation |
Citrullination Carbonylation |
Carbonylation Nitration |
Proteolysis Carbonylation |
Carbonylation Citrullination |
| Tertiary Lymphoid Structure | Yes | Yes | ND | Lymphoid Accumulations | Alveolitis |
| Autoantibodies | ACPA | ACPA | Scl-70 | Fibrillarin | Mesothelial cell |
| MHC association | ND | HLA-SE | HLA-DRB1 | H-2s | ND |
| Diseases | SLE, SSc, RA, ANCA-related vasculitis | Seropositive RA SLE, MS |
SSc | Nephrotic Syndrome | Rheumatological Symptoms |
A comparison of the hypothesized steps leading to autoimmunity or autoimmune disease following exposure to different xenobiotics. Silica, smoking, and solvents exposures are confidently linked to various autoimmune diseases while mercury and asbestos exposures although linked to features of autoimmunity, evidence for causation of autoimmune disease is insufficient.
a
Includes information from animal studies.
ND, not determined.