title: Crohn's disease as an immunodeficiency.
abstract: The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools.
authors.affiliation: Department of Molecular Medicine, University College London, London, WC1E 6JJ, UK. b.hayee@nhs.net
authors.forename: Bu'Hussain
authors.initials: B
authors.lastname: Hayee
authors.forename: Farooq Z
authors.initials: FZ
authors.lastname: Rahman
authors.forename: Gavin
authors.initials: G
authors.lastname: Sewell
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Smith
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Segal
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology