Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. Issue 6 (5th December 2012)

• Record Type: Journal Article
• Authors: Balow, 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
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Issue 6(2013)
• Page Start: 1064
• Page End: 1070
• Publication Date: 2012-12-05
• Subjects: Fever Syndromes -- Inflammation -- Cytokines; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-202082
• Languages: English
• ISSNs: 0003-4967

Abstract

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.