Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino Polyclinic Hospital, Genova, Italy.
Rheumatology and Clinical Immunology Unit, Rheumatology Chair, Spedali Civili, University of Brescia, Brescia, Italy.
Autoimmun Rev. 2020 Dec;19(12):102685. doi: 10.1016/j.autrev.2020.102685. Epub 2020 Oct 22.
Autoimmune rheumatic diseases (ARDs) are chronic conditions with a striking female predominance, frequently affecting women of childbearing age. Sex hormones and gender dimorphism of immune response are major determinants in the multifactorial pathogenesis of ARDs, with significant implications throughout reproductive life. Particularly, pregnancy represents a challenging condition in the context of autoimmunity, baring profound hormonal and immunologic changes, which are responsible for the bi-directional interaction between ARDs outcome and pregnancy course. In the latest years epigenetics has proven to be an important player in ARDs pathogenesis, finely modulating major immune functions and variably tuning the significant gender effects in autoimmunity. Additionally, epigenetics is a recognised influencer of the physiological dynamic modifications occurring during pregnancy. Still, there is currently little evidence on the pregnancy-related epigenetic modulation of immune response in ARDs patients. This review aims to overview the current knowledge of the role of epigenetics in the context of autoimmunity, as well as during physiologic and pathologic pregnancy, discussing under-regarded aspects in the interplay between ARDs and pregnancy pathology. The outline of a new ongoing European project will be presented.
自身免疫性风湿病 (ARDs) 是一种慢性疾病,具有明显的女性优势,常影响育龄妇女。性激素和免疫反应的性别二态性是 ARD 多因素发病机制的主要决定因素,在整个生殖生命过程中具有重要意义。特别是,怀孕在自身免疫的背景下是一种具有挑战性的情况,具有深刻的激素和免疫变化,这是 ARD 结果和妊娠过程之间双向相互作用的原因。近年来,表观遗传学已被证明是 ARD 发病机制中的一个重要因素,它精细地调节主要的免疫功能,并在自身免疫中不同程度地调整显著的性别影响。此外,表观遗传学是怀孕期间发生的生理动态变化的公认影响因素。然而,目前关于 ARD 患者在怀孕期间免疫反应的表观遗传调节的证据很少。这篇综述旨在概述表观遗传学在自身免疫、生理和病理妊娠背景下的作用,并讨论 ARD 和妊娠病理之间相互作用中被忽视的方面。将介绍一个正在进行的欧洲新项目的大纲。