The long and latent road to autoimmunity

摘要

Autoimmune diseases affect nearly 5%of the general population,yet etiology remains poorly understood.Genomic factors are clearly necessary but remain insufficient to explain the loss of tolerance;environmental and stochastic factors fill this gap.This paradigm is indicated by the concordance rates(ranging between 4 and 63%)for autoimmune diseases among monozygotic twins,who share an identical genome,compared to the invariably lower rates in dizygotic twins.The term“exposome”cumulatively refers to the non-hereditary(i.e.,environmental)factors that account for the remaining susceptibility and include endogenous factors such as hormones.Accumulating evidence suggests that exposure to infections,drugs,vaccines,and chemicals may contribute to the loss of tolerance.The mechanisms by which environmental factors can shape the immune system to generate autoimmunity include molecular mimicry,self-antigen modification,bystander activation,and immune reactivity modulation.In all cases,we should first consider the prolonged time between an environmental trigger and the appearance of autoreactivity and subsequent clinical disease.In this special issue,several excellent reviews discuss the potential mechanisms linking environmental factors and autoimmunity.