Browse by author
Lookup NU author(s): Dr Amy AndersonORCiD, Dr Nicola Maney, Dr Dennis LendremORCiD, Julie Diboll, Dr Philip Brown, Dr Graham Smith, Professor John IsaacsORCiD, Dr Arthur PrattORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Objectives: Dysregulated signal transduction and activator of transcription-3 (STAT3) signalling in CD4+ T cells has been proposed as an early pathophysiological event in RA. We sought further evidence for this observation, and to determine its clinical relevance.Methods: Microarray technology was used to measure gene expression in purified peripheral blood CD4+ T cells from treatment-naïve RA patients and disease controls newly recruited from an early arthritis clinic. Analysis focused on 12 previously proposed transcripts, and concurrent STAT3 pathway activation was determined in the same cells by flow cytometry. A pooled analysis of previous and current gene expression findings incorporated detailed clinical parameters and employed multivariate analysis.Results: In an independent cohort of 161 patients, expression of 11 of 12 proposed signature genes differed significantly between RA patients and controls, robustly validating the earlier findings. Differential regulation was most pronounced for the STAT3 target genes PIM1, BCL3 and SOCS3 (>1.3-fold difference; P < 0.005), each of whose expression correlated strongly with paired intracellular phospho-STAT3. In a meta-analysis of 279 patients the same three genes accounted for the majority of the signature's ability to discriminate RA patients, which was found to be independent of age, joint involvement or acute phase response.Conclusion: The STAT3-mediated dysregulation of BCL3, SOCS3 and PIM1 in circulating CD4+ T cells is a discriminatory feature of early RA that occurs independently of acute phase response. The mechanistic and functional implications of this observation at a cellular level warrant clarification.
Author(s): Anderson AE, Maney NJ, Nair N, Lendrem DW, Skelton AJ, Diboll J, Brown PM, Smith GR, Carmody RJ, Barton A, Isaacs JD, Pratt AG
Publication type: Article
Publication status: Published
Journal: Rheumatology
Year: 2019
Volume: 58
Issue: 7
Pages: 1250-1258
Print publication date: 01/07/2019
Online publication date: 08/02/2019
Acceptance date: 13/12/2018
Date deposited: 27/02/2019
ISSN (print): 1462-0324
ISSN (electronic): 1462-0332
Publisher: Oxford University Press
URL: https://doi.org/10.1093/rheumatology/kez003
DOI: 10.1093/rheumatology/kez003
PubMed id: 30753709
Altmetrics provided by Altmetric
