title: The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies.
abstract: OBJECTIVE
  The intestinal microbiome is increasingly implicated in the pathogenesis of ankylosing spondylitis, reactive arthritis, and other diseases collectively known as the spondyloarthropathies (SpAs). In common with other complex inflammatory diseases, SpAs have both a strong genetic and environmental component. Recent genetic studies have highlighted host pathways that may intersect the host-microbiota interaction and offer novel paradigms to understand the pathophysiology of these diseases.
  
  
  RESULTS
  Genetic association studies have identified genes such as RUNX3, PTPEN2, and IL-33 as susceptibility loci for SpAs. Functional studies in humans have extended knowledge of established genetic risk factors for ankylosing spondylitis that include ERAP1, ERAP2, and interleukin-23R. Recent basic research has identified new mechanisms that regulate host immune responses to the microbiota that conceivably may be dysregulated in SpA.
  
  
  CONCLUSIONS
  Intestinal barrier function, deletional tolerance, Th17 signature response, and endoplasmic reticulum stress pathways have been recently linked to SpA. Dysregulated immune responses to the gut microbiota and an altered microbial community structure are shared features of SpA. Although the cause-effect dynamic of this relationship remains equivocal, it nonetheless has major implications for both intestinal and extra-intestinal pathology observed in SpA.
authors.affiliation: aDepartment of Medicine, Oregon Health and Sciences University bLegacy Devers Eye Institute cDepartment of Ophthalmology, Oregon Health and Sciences University dDepartment of Cell and Developmental Biology, Oregon Health and Sciences University, Portland, Oregon, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Asquith
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000626:Aminopeptidases / Q000235:genetics; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D025242:Spondylarthropathies / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology / Q000382:microbiology
chemical_list: D015796:HLA-B27 Antigen; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human