Burska, AN orcid.org/0000-0003-3321-9087, Thu, A, Parmar, R et al. (7 more authors) (2019) Quantifying circulating Th17 cells by qPCR: potential as diagnostic biomarker for rheumatoid arthritis. Rheumatology, 58 (11). pp. 2015-2024. ISSN 1462-0324
Abstract
Objective
The diagnosis of RA patients remains a challenge, especially in ACPA-negative disease. Novel T-cell subsets, particularly Th17 may be useful, although data on Th17 frequency using flow cytometry in RA are conflicting. We investigated whether a novel epigenetic qPCR assay for the quantification of Th17 could differentiate patients with RA from those with symptoms evolving towards an alternative diagnosis.
Methods
We used a qPCR assay measuring the extent of the methylation at a key position in the IL-17 and CD4 genes. Assays were performed on whole blood from 49 healthy controls (HC) and 165 early arthritis clinic patients. Flow cytometry was further used to detect the expression of CXCR4 on Th17 cells.
Results
In 75 inflammatory arthritis patients who progressed to RA, the qPCR assays showed significantly fewer Th17 cells compared with 90 patients who did not (P<0.0001). Regression models demonstrated a high predictive value for RA development (75.8% correct prediction), and particularly for the ACPA-negative group (n = 125) where Th17 and swollen joint count (SJC) were the only predictors (73% correct prediction). The chemokine receptor CXCR4 had significantly higher expression on Th17 from early RA patients (n = 11) compared with HC (n = 15).
Conclusion
The results of the epigenetic qPCR assay showed that low levels of Th17 cells were predictive of developing RA, particularly in the ACPA-negative patients. This could have value for insights into pathogenesis and management. The results suggest the recruitment of Th17 to the inflammatory disease site, consistent with high CXCR4 expression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an author produced version of a paper published in Rheumatology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Th17 cells, rheumatoid arthritis, diagnostic biomarker |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Funding Information: | Funder Grant number EU - European Union 115142 |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Apr 2019 14:27 |
Last Modified: | 12 May 2020 00:38 |
Published Version: | https://academic.oup.com/rheumatology/advance-arti... |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/rheumatology/kez162 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:144482 |