title: Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis.
abstract: RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Institutet, Stockholm, Sweden, anca.catrina@ki.se.
authors.forename: Anca I
authors.initials: AI
authors.lastname: Catrina
authors.affiliation: Division of Rheumatology, University of Colorado, School of Medicine, Aurora, CO and.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, NY, USA.
authors.forename: Jose U
authors.initials: JU
authors.lastname: Scher
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D015551:Autoimmunity / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000502:physiology*; D018928:Immunity, Mucosal / Q000235:genetics / Q000502:physiology; D008297:Male; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D018570:Risk Assessment; D012720:Severity of Illness Index
keywords: break in tolerance; environmental risk factors; genetic susceptibility; microbiome; rheumatoid arthritis