Myeloid dendritic cells correlate with clinical response whereas plasmacytoid dendritic cells impact autoantibody development in rheumatoid arthritis patients treated with infliximab
1 Département de Rhumatologie, CHU Bordeaux, place Amélie Raba-Léon, 33076 Bordeaux, France
2 UMR-CNRS 5164, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France
3 Département de Virologie et d'Immunologie biologique, CHU Bordeaux, place Amélie Raba-Léon, 33076 Bordeaux, France
4 Service de Médecine Interne, CHU Bordeaux, 1 Avenue de Magellan, 33600 Pessac, France
Arthritis Research & Therapy 2009, 11:R100 doi:10.1186/ar2746Published: 29 June 2009
The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), specifically myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab.
Circulating mDC and pDC levels were evaluated by flow cytometry in RA patients (n = 61) and healthy volunteers (n = 30). In RA patients, these levels were measured before and during infliximab therapy. Their counts were correlated to RA disease activity markers and anti-nuclear antibody occurrence. IFNα production was measured by ELISA in serum of RA patients and, in vitro, in supernatant of peripheral blood mononuclear cells stimulated by influenza virus in the presence or absence of infliximab. Statistical evaluations were based on Mann–Whitney tests or Wilcoxon's signed-rank tests.
RA patients with active disease were characterized by a baseline decrease in both circulating pDCs and mDCs. Disease activity markers inversely correlated only with mDC level. This level increased in RA patients responsive to infliximab therapy, to reach the level observed in controls. Conversely, anti-nuclear antibody appearance during infliximab therapy correlated inversely with pDC level and was associated with increased serum IFNα level and circulating plasma cells number. In vitro studies revealed that infliximab kept pDCs in an IFNα secreting state upon viral stimulation allowing differentiation of B cells into anti-nuclear antibody-secreting plasma cells.
This study reveals two distinct roles for pDC and mDC in RA. Circulating mDCs mainly contribute to RA activity, whereas pDCs seem to be involved in appearance of anti-nuclear antibodies under infliximab therapy through the ability of this drug to keep pDCs in an IFNα secreting state.