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Psoriatic arthritis
Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
  1. Sarah M Wade1,2,
  2. Mary Canavan1,
  3. Trudy McGarry1,2,
  4. Candice Low2,
  5. Siobhan C Wade1,
  6. Ronan H Mullan3,
  7. Douglas J Veale2,
  8. Ursula Fearon1
  1. 1 Molecular Rheumatology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
  2. 2 St Vincent's University Hospital, Dublin Academic Health Care and University College Dublin, Dublin 4, Ireland
  3. 3 Department of Rheumatology, Tallaght University Hospital, Dublin 24, Ireland
  1. Correspondence to Professor Douglas J Veale, Molecular Rheumatology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D2 4, Ireland; douglas.veale{at}ucd.ie

Abstract

Objective This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy.

Methods PsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Frequencies of polyfunctional CD4, CD8, T-helper 1 (Th1), Th17 and exTh17 cells, using CD161 as a marker of Th17 plasticity, were determined by flow cytometry in matched PsA synovial tissue and peripheral blood. Synovial T-cell polyfunctionality was assessed in relation to Disease Activity in PSoriatic Arthritis (DAPSA) and in synovial cell suspensions cultured with a current mode of treatment, phosphodiesterase 4 (PDE4) inhibitor.

Results PsA synovial tissue infiltrating CD4+ T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p<0.01), Th17-GM-CSF+/TNF+/IL-17+ (r=0.6, p<0.057) and exTh17-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF+TNFα+IL-17A+ or/IFN-γ+-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor.

Conclusion These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.

  • psoriatic arthritis
  • synovial tissue
  • polyfunctional t-cells

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/annrheumdis-2018-214138

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    Footnotes

    • Handling editor Professor Josef S Smolen

    • Contributors SMW, MC, DJV, UF: developed the concept and wrote the paper. SMW, MC, TMG, SCW, CL, RHM, DJV, UF: generated and interpreted the data. UF, DJV: supervised the project. All authors critically reviewed and edited the paper.

    • Funding This study was sponsored by IRCSET and Arthritis Ireland.

    • Competing interests None declared.

    • Patient consent for publication Obtained.

    • Ethics approval Ethical approval to conduct this study was granted by St Vincent’s Healthcare Group Medical Research and Ethics Committee and the Tallaght Hospital/St James's Hospital Joint Research Ethics Committee. All experiments were performed in accordance with these guidelines and regulations.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data from this study were published in the article or in the online supplementary information.