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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\u2010DR genetic variants in triggering antigen\u2010specific 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\u2010mediated 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 \u2018personalized prevention\u2019. We believe that the progress described here for RA will be of relevance for research and practice also in other immune\u2010mediated diseases.<\/jats:p>","DOI":"10.1111\/joim.13058","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T10:42:15Z","timestamp":1584355335000},"page":"514-533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-6186","authenticated-orcid":false,"given":"L.","family":"Klareskog","sequence":"first","affiliation":[{"name":"From the Division of Rheumatology Department of Medicine Karolinska Institutet and Karolinska University Hospital (Solna) Stockholm 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