Increased FcgammaRII expression and aberrant tumour necrosis factor alpha production by mature dendritic cells from patients with active rheumatoid arthritis.
OBJECTIVE
To investigate potential differences in phenotype and behaviour of immature (iDC) and mature dendritic cells (mDC) from patients with RA and healthy subjects.


METHODS
iDC and mDC were derived from blood monocytes of patients with RA and healthy controls following standardised protocols. FACS was used to analyse expression of FcgammaRI, II, and III and molecules to characterise DC. Discrimination between FcgammaRIIa and FcgammaRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFalpha production by iDC and mDC upon FcgammaR dependent stimulation was compared between patients with RA and controls by ELISA.


RESULTS
iDC from patients with active RA but not from patients with inactive RA or healthy controls markedly up regulated FcgammaRII. mDC from patients with active RA also lacked the physiological down regulation of FcgammaRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcgammaRII in RA-especially marked for FcgammaRIIb. FcgammaR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFalpha production by DC from healthy subjects, but significantly decreased TNFalpha by DC from patients with RA. Overlapping expression patterns between FcgammaRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcgammaRIIb.


CONCLUSIONS
The presence and altered characteristics of DC during active RA suggest that DC help to modulate autoimmunity in RA. Further studies should elucidate the role of local factors in altering the function of DC in RA and in increasing expression of FcgammaRII.
Radstake
T R D J
TR
Department of Rheumatology, University Medical Centre Nijmegen, Geertgroote plein 8, 6500 HB Nijmegen, The Netherlands. T.radstake@reuma.umcn.nl.
Blom
A B
AB
Slöetjes
A W
AW
van Gorselen
E O F
EO
Pesman
G J
GJ
Engelen
L
L
Torensma
R
R
van den Berg
W B
WB
Figdor
C G
CG
van Lent
P L E M
PL
Adema
G J
GJ
Barrera
P
P
D000936:Antigen-Antibody Complex / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000276:immunology
D000936:Antigen-Antibody Complex; D012333:RNA, Messenger; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha