Myeloid dendritic cells correlate with clinical response whereas plasmacytoid dendritic cells impact autoantibody development in rheumatoid arthritis patients treated with infliximab.
BACKGROUND
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.


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 antibody occurrence. IFNalpha 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.


RESULTS
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 IFNalpha level and circulating plasma cells number. In vitro studies revealed that infliximab kept pDCs in an IFNalpha 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 IFNalpha secreting state.
Richez
Christophe
C
Département de Rhumatologie, CHU Bordeaux,Place Amélie Raba-Léon, 33076 Bordeaux, France. christophe.richez@mac.com
Schaeverbeke
Thierry
T
Dumoulin
Chantal
C
Dehais
Joël
J
Moreau
Jean-François
JF
Blanco
Patrick
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000069285:Infliximab