Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Centre for Epidemiology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, UK.
Nat Rev Rheumatol. 2018 Apr 20;14(5):255-268. doi: 10.1038/nrrheum.2018.48.
Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic processes in the various idiopathic inflammatory myopathy (IIM) phenotypes (known collectively as myositis) have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in some populations, and several genetic variants associated with other autoimmune diseases have been identified as IIM risk factors. Environmental risk factors are less well studied than genetic factors but might include viruses, bacteria, ultraviolet radiation, smoking, occupational and perinatal exposures and a growing list of drugs (including biologic agents) and dietary supplements. Disease mechanisms vary by phenotype, with evidence of shared innate and adaptive immune and metabolic pathways in some phenotypes but unique pathways in others. The heterogeneity and rarity of the IIMs make advancements in diagnosis and treatment cumbersome. Novel approaches, better-defined phenotypes, and international, multidisciplinary consensus have contributed to progress, and it is hoped that these methods will eventually enable therapeutic intervention before the onset or major progression of disease. In the future, preemptive strategies for IIM management might be possible.
自身免疫性疾病是由于基因与环境相互作用导致的慢性炎症而发展起来的。然而,自身免疫性疾病的演变机制仍知之甚少。在各种特发性炎性肌病(IIM)表型(统称为肌炎)中发现的新的风险因素和发病机制,为理解这些疾病提供了创新的方法。在某些人群中,HLA8.1 祖先单倍型是主要 IIM 表型的关键风险因素,并且已经确定了与其他自身免疫性疾病相关的几种遗传变异是 IIM 的风险因素。环境风险因素的研究不如遗传因素充分,但可能包括病毒、细菌、紫外线辐射、吸烟、职业和围产期暴露以及越来越多的药物(包括生物制剂)和膳食补充剂。疾病机制因表型而异,一些表型中存在共享的先天和适应性免疫及代谢途径,而其他表型中则存在独特的途径。IIM 的异质性和罕见性使得诊断和治疗的进展变得复杂。新的方法、更明确的表型以及国际多学科共识都有助于取得进展,人们希望这些方法最终能够在疾病发作或主要进展之前进行治疗干预。将来,可能会有针对 IIM 管理的预防策略。