title: NOD2-associated diseases: Bridging innate immunity and autoinflammation.
abstract: NOD2 is an intracellular microbial sensor of the innate immune system that can act as a potent activator and regulator of inflammation. Mutations in the gene encoding NOD2 in humans have been associated with Crohn's disease (CD), Blau syndrome (BS), and early onset sarcoidosis (EOS). These diseases have in common features of dysregulated inflammation, but have very distinct phenotypes, which have been hypothesized to result from either loss-of-function (CD) or gain-of-function (BS/EOS) mutations. Here we describe an infant with early onset sarcoidosis who presented with systemic inflammation and disseminated granulomatous disease, including the triad of granulomatous arthritis, uveitis and dermatitis, as well as unusual gastrointestinal tract granulomas. The patient had a susceptibility polymorphism of NOD2 previously described in CD, but not in BS or EOS. We discuss the complex role of NOD2 in innate immunity to microbes and the clinical consequences of disturbances in this system.
authors.affiliation: Children's Hospital Boston, MA 02115, USA. arturo.borzutzky@childrens.harvard.edu
authors.forename: Arturo
authors.initials: A
authors.lastname: Borzutzky
authors.forename: Ari
authors.initials: A
authors.lastname: Fried
authors.forename: Janet
authors.initials: J
authors.lastname: Chou
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: Susan
authors.initials: S
authors.lastname: Kim
authors.forename: Fatma
authors.initials: F
authors.lastname: Dedeoglu
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006099:Granuloma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007223:Infant; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*; D012507:Sarcoidosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein