Dysregulated Fc receptor function in active rheumatoid arthritis
2014 (English)In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 162, no 1 Pt A, 200-206 p.Article in journal (Refereed) Published
Given the critical role of Fc gamma receptors (FcgammaR) as primary targets for autoantibody-mediated effects an important issue is how the FcgammaR pathway is affected in autoimmune disorders. Here we investigated the FcgammaR 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 FcgammaRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcgammaR 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 FcgammaRI, II and cell surface IgG concurrently with impaired FcgammaR 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 FcgammaR function and had increased FcgammaRIIb expression together with elevated FcgammaRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcgammaRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcgammaR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcgammaR function controlling effect is suggested by the increased inhibitory FcgammaRIIb in non-active RA.
Place, publisher, year, edition, pages
2014. Vol. 162, no 1 Pt A, 200-206 p.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-239373DOI: 10.1016/j.imlet.2014.08.016ISI: 000347753700026PubMedID: 25194756OAI: oai:DiVA.org:uu-239373DiVA: diva2:774814