Published online 2019 Jun 5

Considerable evidence indicates that autoimmune disease expression depends on both genetic and environmental factors.  These results support a multihit model of autoimmunity, where exposure to different environmental factors acting on distinct immunostimulatory pathways complements limited genetic predisposition and increases the risk of autoimmunity above a critical threshold.

A key question raised by the present study relates to the mechanistic basis of the synergisms between virus and silica in autoimmunity. Considering the essential role of the innate immune system in spontaneous lupus, we hypothesize that virus and silica might contribute by inducing distinct innate immune pathways that, acting in concert, more efficiently promote inflammatory cell activation both in the lungs and systemically, break of tolerance, and autoimmune disease onset and severity.

In conclusion, the present study provides evidence that a chronic viral infection can significantly enhance the risk of developing autoimmunity following silica exposure and vice versa. Thus, susceptibility to lupus, and likely other autoimmune diseases, appears to depend on the additive effects of a sufficient number of genetic and environmental factors to which an individual is progressively exposed throughout life.