Myeloid dendritic cells correlate with clinical response whereas plasmacytoid dendritic cells impact autoantibody development in rheumatoid arthritis patients treated with infliximab
IntroductionThe objective of our study was to identify the significance of the sub-types of dendritic cell (DC), specifically myeloid DC (mDC) and plasmacytoid DC (pDC), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab.
Methods: 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 antibodies occurrence. Interferon-a 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 presence or absence of infliximab.
Statistical evaluations were based on Mann-Whitney tests or Wilcoxon's signed rank tests.
Results: RApatients 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 antibodies appearance during infliximab therapy correlated inversely with pDCs level and was associated with increased serum interferon-a level and circulating plasma cells number.
In vitro studies revealed that infliximab kept pDCs in an interferon-a secreting state upon viral stimulation allowing differentiation of B cells into anti-nuclear antibody-secreting plasma cells.
Conclusions: 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 interferon-a secreting state.
Author: Christophe RichezThierry SchaeverbekeChantal DumoulinJoel DehaisJean-Francois MoreauPatrick Blanco
Credits/Source: Arthritis Research &Therapy 2009, 11:R100
Published on: 2009-06-29
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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