Abstract
IntroductionThe 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.MethodsCirculating 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.ResultsRA 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.ConclusionsThis 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.
Highlights
The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), myeloid Dendritic cells (DCs) and plasmacytoid DCs, in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab
Circulating myeloid dendritic cells (mDCs) mainly contribute to RA activity, whereas plasmacytoid dendritic cells (pDCs) seem to be involved in appearance of antinuclear antibodies under infliximab therapy through the ability of this drug to keep pDCs in an IFNα secreting state
Blood dendritic cell subsets in RA and their correlation with disease activity To better delineate the involvement of known DC subsets in RA pathogenesis, we compared the number of circulating CD11c+HLA-DR+CD123- mDCs and CD11c-HLADR+CD123+ pDCs in peripheral blood from 61 active RA patients and from 30 healthy volunteers
Summary
The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab. Two DC subsets, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), have been identified in humans These DC subsets recognize different microbial pathogens through specific receptors, which in turn induce different types of innate and adaptive immune responses [1]. In systemic lupus erythematosus (SLE), an autoimmune disease characterized by the presence of an autoimmune reaction against nuclear components, pDCs secrete large amounts of IFNα This secretion promotes the differentiation of monocytes into mDCs. This secretion promotes the differentiation of monocytes into mDCs These mDCs capture circulating nucleic acid-containing bodies and activate autoreactive T cells and B cells, leading to the increased production of autoantibodies by plasma cells [3,4]
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