抄録
Autoimmunity results from interactions of genetic factors and environmental factors, which include a variety of components such as infection, xenobiotics (drug, chemicals, vaccine, food, etc), geo-climate factors and others.
The mechanisms on how environmental factors trigger autoimmunity are heterogeneous and incompletely understood, however, non-specific immune stimulation (adjuvant effects) of xenobiotics may increase the risk to develop autoimmunity. Most vaccines contain adjuvants in addition to microbial components, to enhance immune responses, which may also trigger autoimmunity. A single intraperitoneal (ip) injection of an adjuvant oil pristane, a component of mineral oil, induces a type-I interferon and TLR7-dependent lupus-like autoimmune syndrome in mice. Ip injection of incomplete Freund’s adjuvant (mineral oil) and squalene (a main component of MF59 adjuvant used in human vaccines) also induced lupus autoantibodies. Mineral oils are generally considered inert, however, they also can induce arthritis in animals. Human exposure to mineral oils at work environment was associated with an increased risk to develop rheumatoid arthritis. Injection of mineral oil as a cosmetic procedure is common in Mexico, however, development of an autoimmune syndrome induced by adjuvants (ASIA) is reported. These patients had rheumatologic symptoms and antinuclear antibodies, anti-U1RNP, and -Su/Argonaute2, similar to animal models of mineral oil-induced autoimmunity.
For certain chemicals/drugs, induction of autoantibodies to the target molecule of the chemical/drug is shown. Mercury exposure induces anti-nucleolar antibodies that recognize a mercury-binding protein fibrillarin(U3RNP) in mice and human. Ribavirin used in hepatitis C viral infection induced autoantibodies to cytoplasmic rods and rings structure, which recognize the target molecule of the ribavirin, inosine monophosphate dehydrogenase (IMPDH).
Adjuvants and certain xenobiotics may induce autoimmunity via non-specific activation of the immune system but also by modifying specific antigens.
