Background Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can induce either immunity or tolerance. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) represent the 2 major subsets of DCs, with human pDCs defined as CD4+CD11c-CD123hiCD1c-CD303+HLADR+ cells, and mDCs defined as CD4+CD1c+CD123loCD303-CD45RO-HLADR+ cells. Some studies reported that patients with therapy-induced remission of rheumatoid arthritis (RA) exhibited higher numbers of circulating pDCs.
Objectives Indeed, in vivo effects of IL-6 inhibition on DCs are partially unknown. Tocilizumab (TCZ) is the first therapeutic agent targeting IL-6 to be effective in RA. Our aim was to monitor the changes in circulating mDCs and pDCs during TCZ therapy in patients with RA.
Methods DC subsets were characterized by flow cytometry in the peripheral blood of patients with RA (n=15) and in healthy volunteers (n=10). In patients with RA, these levels were measured before and during TCZ therapy (8 mg/kg every 4 weeks). Response to TCZ therapy was evaluated at 12 weeks. All the patients fulfilled the 1987 ACR criteria for RA. At baseline, the mean DAS28 score was 5.2 (±1.3). At 3 months, 9 patients were classified as responders (DAS28 1.8±0.8) and 6 patients were classified as non-responders (DAS28 4.0±0.4). Statistical analyses were performed by Mann-Whitney U tests or Wilcoxon signed-rank tests.
Results At baseline, patients with active RA were characterized by a significantly decrease frequency of circulating pDCs compared to healthy donors (40.2% vs 60.9%; p<0.01). After 3 months of TCZ therapy, pDC frequency has not changed (48.5% vs 40.2%) while mDC frequency decrease significantly (31.1% vs 22.3%; p<0.05). Moreover, TCZ-treated patients who reached low disease activity at Week 12 had significant increase frequency of pDC (52.0% vs 38.7%; p<0.05) as compared with non-responders patients (43.2% vs 42.5%).
Conclusions Our study reveals an increased frequency of circulating pDC in responder patients to TCZ therapy. We previously demonstrated that the clinical response was also associated with increased frequencies of CD39+ Treg cells. Our results suggest a crosstalk between DC and Tregs to restore/induce tolerance.
Disclosure of Interest None declared
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