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THU0500 Cytokine Production Identifies A Subset of Rheumatoid Arthritis Patients T Lymphocytes That is Associated with Responsiveness to Biologic Anti-TNF-Alpha Agents
  1. J. Bystrom1,
  2. T. Taher1,
  3. M. Al-Bogami1,
  4. S. Alzabin2,
  5. S. Kelly1,
  6. P. Mangat3,
  7. R. Williams2,
  8. A. Jawad1,
  9. R. Mageed1
  1. 1William Harvey Research Institute, Barts School of Medicine, QMUL, London
  2. 2Kennedy Institute of Rheumatology, Oxford University, Oxford
  3. 3Department of Rheumatology, Royal Free Hospital, London, United Kingdom

Abstract

Background Biologic anti-TNFα agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). However 30-40% of RA patients do not respond to treatment with these agents. Our studies have suggested that non-responsiveness is due to increased frequency of Th17 lymphocytes.

Objectives To determine if the frequency of T-lymphocyte subsets prior to treatment predicts the response to anti-TNFa agents.

Methods Blood from 70 RA patients prior to and at 4 and 12 weeks post treatment were obtained and level of cytokines in plasma and culture supernatant of stimulated T lymphocytes and monocytes determined. Response to treatment was assessed after 12 weeks by changes in DAS28. Enriched T lymphocytes were stimulated with anti CD3/CD28 and monocytes with LPS. Cytokines levels were determined assessed using a multiplex protocol (MSD technologies). Surface markers and intracellular cytokines expressed by the cells were analysed by FACS.

Results Prior to treatment, responder patients had significantly more TNFα and GM-CSF-producing T lymphocytes than non-responder patients. Intracellular staining revealed that both cytokines were primarily produced by the same T lymphocytes in responder patients. The frequency of TNFα/GM-CSF-producing T lymphocytes was not associated with age nor with gender but patients with high frequency tended to have relatively low DAS28. Interestingly, whilst TNFα/GM-CSF-producing T lymphocytes in responder patient could also produce IL-17, the production of this cytokine was primarily confined to a distinct subset of T lymphocyte in non-responder patients. Finally, plasma levels of GM-CSF were significantly higher in responders compared with non-responders patients prior to treatment.

Conclusions A subset of CD4+ T lymphocytes that produces TNFα and GM-CSF is present at higher frequencies in the blood of RA patients that respond to biologic anti-TNFα agents than in non-responders. This is in contrast to non-responder patients who have higher frequencies of Th17 lymphocytes. Our data may suggest that RA patients could be stratified into responder and non-responder patients to treatment with biologic anti-TNFα based on the T lymphocyte subset that is involved in their disease. Further, measurement of GM-CSF and IL-17 could be useful in identifying responder/non-responder patients prior to treatment.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.4637

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