Increased FcγRII expression and aberrant tumour necrosis factor α production by mature dendritic cells from patients with active rheumatoid arthritis

Abstract

Objectives: 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 FcγRI, II, and III and molecules to characterise DC. Discrimination between FcγRIIa and FcγRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFα production by iDC and mDC upon FcγR 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 FcγRII. mDC from patients with active RA also lacked the physiological down regulation of FcγRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcγRII in RA-especially marked for FcγRIIb. FcγR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFα production by DC from healthy subjects, but significantly decreased TNFα by DC from patients with RA. Overlapping expression patterns between FcγRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcγRIIb. Conclusion: 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 FcγRII.