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A1.2 Prominent role of pathogenic memory CCR6+ TH17 cell populations in the pathogenesis of ACPA+ patients with rheumatoid arthritis
  1. SMJ Paulissen1,2,
  2. JP van Hamburg1,2,
  3. N Davelaar1,2,
  4. H Vroman1,3,
  5. W Dankers1,2,
  6. JMW Hazes1,
  7. PHP de Jong1,
  8. E Lubberts1,2
  1. 1Department of Rheumatology University Medical Centre, Rotterdam, The Netherlands
  2. 2Department of Immunology University Medical Centre, Rotterdam, The Netherlands
  3. 3Department of Pulmonary Medicine Erasmus MC, University Medical Centre, Rotterdam, The Netherlands

Abstract

Background and objectives Patients with rheumatoid arthritis (RA) positive for serum anti-citrullinated protein antibodies (ACPAs) have a worse disease course than ACPA- patients. Association of ACPA and HLA-DRB1 suggests the involvement of T cells in ACPA+ RA. Therefore we examined possible differences in memory CD4+ T (Th) cell distribution between ACPA+ and ACPA- patients and their functional relevance.

Materials and methods Th cell distribution profiles from ACPA+ and ACPA- patients with early RA were generated based on chemokine receptor, cytokine and transcription factor expression. On the basis of CXCR3 and CCR4 expression, four CCR6+ subpopulations were distinguished: Th17, Th17.1, CCR4/CXCR3 double positive (DP) and double negative (DN) cells. These Th cell populations were analysed for their pathological potential.

Results ACPA+ patients had higher proportions of peripheral CCR6+ Th cells, notably Th22, Th17.1 and DP cells. All CCR6+ subpopulations were also present in RA synovial fluid. These subpopulations shared Th17 characteristics including RORC and CD161 expression. However, expression of IL-17A, IL-17F, IFNg and the Th1-associated transcription factor TBX21 differed markedly between CCR6+ subpopulations. Nevertheless, all CCR6+ Th cell subpopulations showed higher pathological activity than naive and Th1 cells, as they were more effective in stimulating IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression by synovial fibroblasts. Interestingly, CCR6+ Th populations are inverse correlated with disease duration in ACPA- patients but not in ACPA+ patients.

Conclusions ACPA+ and ACPA- patients can be distinguished by differences in pathogenic memory CCR6+ Th cell proportions, suggesting that these cells are involved in the worse disease course observed in ACPA+ RA.

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