Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts.
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 patte...
| Published in: | Annals of the Rheumatic Diseases Vol. 72; no. 6; pp. 1064 - 1071 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Elsevier B.V.
Jun2013
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104287404&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104287404 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00034967 ANR jtl: Annals of the Rheumatic Diseases issn: 00034967 maglogo: N pubinfo: dt: Jun2013 vid: 72 iid: 6 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 104287404 NLM23223423 2012117046 10.1136/annrheumdis-2012-202082 NLM23223423 PMC4174357 104287404 ppf: 1064 ppct: 7 formats: tig: atl: Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. aug: au: Balow Jr, James E Ryan, John G Chae, Jae Jin Booty, Matthew G Bulua, Ariel Stone, Deborah Sun, Hong-Wei Greene, James Barham, Beverly Goldbach-Mansky, Raphaela Kastner, Daniel L Aksentijevich, Ivona Balow, James E Jr affil: Inflammatory Disease Section, National Human Genome Research Institute (NHGRI), Bethesda, Maryland 20892-1820, USA sug: subj: Antirheumatic Agents Therapeutic Use Autoimmune Diseases Proteins Therapeutic Use RNA Adult Autoimmune Diseases Drug Therapy Case Control Studies Child Gene Expression Profiling Human Microarray Analysis Models, Biological Severity of Illness Indices Adult: 19-44 years Child: 6-12 years ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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