The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis.,Journal of Internal Medicine

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The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis.
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2020-04-29 , DOI: 10.1111/joim.13058
L Klareskog ₁ , J Rönnelid ₂ , S Saevarsdottir _{3,

4} , L Padyukov ₁ , L Alfredsson ₅

Affiliation

The current review uses rheumatoid arthritis (RA) as a prominent example for how studies on the interplay between environmental and genetic factors in defined subsets of a disease can be used to formulate aetiological hypotheses that subsequently can be tested for causality using molecular and functional studies. Major discussed findings are that exposures to airways from many different noxious agents including cigarette smoke, silica dust and more interact with major susceptibility genes, mainly HLA-DR genetic variants in triggering antigen-specific immune reactions specific for RA. We also discuss how several other environmental and lifestyle factors, including microbial, neural and metabolic factors, can influence risk for RA in ways that are different in different subsets of RA.The description of these processes in RA provides the best example so far in any immune-mediated disease of how triggering of immunity at one anatomical site in the context of known environmental and genetic factors subsequently can lead to symptoms that precede the classical inflammatory disease symptoms and later contribute also to the classical RA joint inflammation. The findings referred to in the review have led to a change of paradigms for very early therapy and prevention of RA and to efforts towards what we have named 'personalized prevention'. We believe that the progress described here for RA will be of relevance for research and practice also in other immune-mediated diseases.

中文翻译：

差异的重要性；关于环境及其与基因的相互作用以及类风湿关节炎的免疫力。

本篇综述使用类风湿关节炎（RA）作为一个突出的例子，说明如何将环境和遗传因素在疾病的特定亚类中相互作用的研究用于提出病因假说，随后可以使用分子和功能研究对其因果关系进行检验。讨论的主要发现是，许多不同的有毒物质（包括香烟烟雾，二氧化硅粉尘）暴露于呼吸道，并且更多地与主要的易感基因（主要是HLA-DR遗传变异）相互作用，触发针对RA的抗原特异性免疫反应。我们还将讨论其他几种环境和生活方式因素，包括微生物，神经和代谢因素如何以不同的RA子集不同的方式影响RA的风险。迄今为止，RA中这些过程的描述在任何免疫介导的疾病中提供了最好的例子，即在已知的环境和遗传因素的背景下，在一个解剖部位触发免疫继而可导致典型的炎症性疾病症状之前的症状，以及后来也导致了经典的RA关节发炎。审查中提到的发现导致非常早期的RA治疗和预防范式发生了变化，并朝着我们称之为“个性化预防”的方向努力。我们认为，此处描述的RA进展与其他免疫介导疾病的研究和实践也具有相关性。

更新日期：2020-04-29

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