Risk Factors and Disease Mechanisms in Myositis

Frederick W Miller, Janine Lamb, Jens Schmidt, Kanneboyina Nagaraju

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Abstract

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 idiopathic inflammatory myopathy (IIM) phenotypes have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in white populations, and genetic risk variants for other autoimmune diseases have been identified as IIM risk factors. Environmental risk factors are less studied but might include viruses, bacteria, ultraviolet radiation, smoking, occupational and perinatal exposures and a growing list of drugs, biologics, and dietary supplements. Disease mechanisms vary by phenotype, with evidence for 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 hopefully these methods can eventually enable therapeutic intervention before the onset or major progression of disease. In the future, preemptive strategies to IIM management might be possible.
Original languageEnglish
Pages (from-to)255-268
JournalNature Reviews Rheumatology
Volume14
Early online date20 Apr 2018
DOIs
Publication statusPublished - 2018

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