title: Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts.
abstract: OBJECTIVE
  To analyse gene expression patterns and to define a specific gene expression signature in patients with the severe end of the spectrum of cryopyrin-associated periodic syndromes (CAPS). The molecular consequences of interleukin 1 inhibition were examined by comparing gene expression patterns in 16 CAPS patients before and after treatment with anakinra.
  
  
  METHODS
  We collected peripheral blood mononuclear cells from 22 CAPS patients with active disease and from 14 healthy children. Transcripts that passed stringent filtering criteria (p values≤false discovery rate 1%) were considered as differentially expressed genes (DEG). A set of DEG was validated by quantitative reverse transcription PCR and functional studies with primary cells from CAPS patients and healthy controls. We used 17 CAPS and 66 non-CAPS patient samples to create a set of gene expression models that differentiates CAPS patients from controls and from patients with other autoinflammatory conditions.
  
  
  RESULTS
  Many DEG include transcripts related to the regulation of innate and adaptive immune responses, oxidative stress, cell death, cell adhesion and motility. A set of gene expression-based models comprising the CAPS-specific gene expression signature correctly classified all 17 samples from an independent dataset. This classifier also correctly identified 15 of 16 post-anakinra CAPS samples despite the fact that these CAPS patients were in clinical remission.
  
  
  CONCLUSIONS
  We identified a gene expression signature that clearly distinguished CAPS patients from controls. A number of DEG were in common with other systemic inflammatory diseases such as systemic onset juvenile idiopathic arthritis. The CAPS-specific gene expression classifiers also suggest incomplete suppression of inflammation at low doses of anakinra.
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute (NHGRI), Bethesda, Maryland 20892-1820, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Balow
authors.forename: John G
authors.initials: JG
authors.lastname: Ryan
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: Chae
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Booty
authors.forename: Ariel
authors.initials: A
authors.lastname: Bulua
authors.forename: Deborah
authors.initials: D
authors.lastname: Stone
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.forename: James
authors.initials: J
authors.lastname: Greene
authors.forename: Beverly
authors.initials: B
authors.lastname: Barham
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
authors.forename: Ivona
authors.initials: I
authors.lastname: Aksentijevich
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D046228:Microarray Analysis; D008957:Models, Genetic; D012720:Severity of Illness Index; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein