title: NOD2-associated autoinflammatory disease: a large cohort study.
abstract: OBJECTIVE
  The aims of the study were to characterize the genotype profile of nucleotide-binding oligomerization domain containing 2 (NOD2)-associated autoinflammatory disease (NAID) and to report an extended study of the disease.
  
  
  METHODS
  A total of 143 adult patients presented with clinical phenotypes suspicious for NAID and all were genotyped for NOD2 sequence variants. The genotype frequencies were compared between our cohort and literature reports. These patients were divided into two groups predicated on the presence or absence of NOD2 variants.
  
  
  RESULTS
  Of the 143 patients, 67 (47%) carry NOD2 variants; the genotype frequency was significantly higher among our cohort than in the historical healthy controls. Fifty-four of the 67 carriers of NOD2 variants had NAID, which has a genotype profile that is somewhat different from Crohn's disease. All NAID patients were non-Jewish whites and 69% were women. The median age at onset was 33.5 years and the median disease duration at diagnosis was 10.7 years. NAID was sporadic in 93% of cases. Patients typically presented with periodic fever, dermatitis and inflammatory arthritis. As compared with the NOD2 variant-negative patients, the skin disease more typically manifested as erythematous patches or plaques on the trunk. Oligopolyarthritis/-arthralgia was common, with characteristic distal lower extremity swelling. Associated NOD2 variants were primarily IVS8(+158) or compound IVS8(+158) and R702W.
  
  
  CONCLUSIONS
  This study underscores the NOD2 genotype association with NAID, which is a genetically complex multisystem disorder. It differs phenotypically from Crohn's disease with a distinct genotype profile. This disease may be more common than initially thought.
authors.affiliation: Department of Rheumatic and Immunologic Disease, qingpingyao@yahoo.com.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Rheumatic and Immunologic Disease.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Pathobiology.
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Department of Molecular Pathology.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Lacbawan
authors.affiliation: Genomic Medicine Institute, and.
authors.forename: Rocio
authors.initials: R
authors.lastname: Moran
authors.affiliation: Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D056660:Hereditary Autoinflammatory Diseases / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Crohn’s disease; IVS8+158; NOD2-associated autoinflammatory disease; nucleotide-binding oligomerization domain containing 2 (NOD2)