title: Dysregulated Fc receptor function in active rheumatoid arthritis.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Sofia E
authors.initials: SE
authors.lastname: Magnusson
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Wennerberg
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Matt
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Lindqvist
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. Electronic address: Sandra.Kleinau@icm.uu.se.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; C499173:FCGR2B protein, human; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D048069:Tumor Necrosis Factors
keywords: Autoimmunity; Fc receptor; IgG; Monocyte; Rheumatoid arthritis; Tumor necrosis factor alpha