Dysregulated Fc receptor function in active rheumatoid arthritis.

Given the critical role of Fc gamma receptors (FcγR) as primary targets for autoantibody-mediated effects an important issue is how the FcγR pathway is affected in autoimmune disorders. Here we investigated the FcγR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcγRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcγR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcγRI, II and cell surface IgG concurrently with impaired FcγR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcγR function and had increased FcγRIIb expression together with elevated FcγRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcγRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcγR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcγR function controlling effect is suggested by the increased inhibitory FcγRIIb in non-active RA.

Magnusson SE ，Wennerberg E ，Matt P ，Lindqvist U ，Kleinau S ... -  《-》

Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins.

Laurent L ，Clavel C ，Lemaire O ，Anquetil F ，Cornillet M ，Zabraniecki L ，Nogueira L ，Fournié B ，Serre G ，Sebbag M ... -  《-》

A shift in the balance of inhibitory and activating Fcgamma receptors on monocytes toward the inhibitory Fcgamma receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis.

Wijngaarden S ，van de Winkel JG ，Jacobs KM ，Bijlsma JW ，Lafeber FP ，van Roon JA ... -  《ARTHRITIS AND RHEUMATISM》

Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR Function and Disease in Early Rheumatoid Arthritis That Can Be Regulated by Anti-Rheumatic Treatment.

Matt P ，Lindqvist U ，Kleinau S 《-》

Up-regulation of CD64-expressing monocytes with impaired FcγR function reflects disease activity in polyarticular psoriatic arthritis.

Matt P ，Lindqvist U ，Kleinau S 《-》