title: A new category of autoinflammatory disease associated with NOD2 gene mutations.
abstract: BACKGROUND
  Autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high titers of autoantibodies or antigen-specific T cells, and derive from genetic variants of the innate immune system. This study characterized a cohort of patients with similar phenotypes and nucleotide oligomerization domain 2 (NOD2) gene mutations.
  
  
  METHODS
  Diagnostically challenging patients with the following clinical and genetic characteristics were prospectively studied between January 2009 and April 2011: periodic fever, dermatitis, polyarthritis, serositis, negative serum autoantibodies and additional positive NOD2 IVS8+158 gene mutation. Genetic testing for gene mutations of NOD2, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) and familial Mediterranean fever (FMF) was performed.
  
  
  RESULTS
  All seven patients with the disease were Caucasians, with four being male. The mean age at disease onset was 40.7 years and disease duration was 3.2 years. These patients characteristically presented with periodic fever, dermatitis and inflammatory polyarthritis. There were gastrointestinal symptoms in three patients, granulomas of the skin and gut in two, and recurrent chest pain in two, with one having pleuritis and pericarditis. Three patients had sicca-like symptoms. Five patients had increased acute phase reactants. All seven patients had negative tests for autoantibodies but carried the NOD2 gene mutation IVS8+158 with four having concurrent R702W mutation.
  
  
  CONCLUSIONS
  Our cohort may represent a new disease category of autoinflammatory disease with characteristic clinical phenotypes and genotypes. It may somewhat resemble pediatric Blau's syndrome.
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. yaoq@ccf.org
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yao
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Philip
authors.initials: P
authors.lastname: Cusumano
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Bose
authors.forename: Melissa
authors.initials: M
authors.lastname: Piliang
authors.forename: Bijal
authors.initials: B
authors.lastname: Jayakar
authors.forename: Le-Chu
authors.initials: LC
authors.lastname: Su
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000145:classification* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056660:Hereditary Autoinflammatory Diseases / Q000145:classification* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein