{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:19:15Z","timestamp":1791011955837,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T00:00:00Z","timestamp":1164672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Fc\u03b3 receptors (Fc\u03b3Rs) recognize immune complexes (ICs) and coordinate the immune response by modulating the functions of dendritic cells (DCs). The purpose of this study was to unravel the role of the inhibitory Fc\u03b3RIIb in rheumatoid arthritis (RA) by studying the effect of the <jats:italic>FCGR2B<\/jats:italic> 695T&gt;C polymorphism on susceptibility to RA, severity of the disease, and DC function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genotyping was performed in RA patients (n = 246) and healthy blood donors (n = 269). The patients' demographic data, disease severity, and disease progression were assessed over a followup of 6 years. DCs were cultured for flow cytometry to determine the expression of Fc\u03b3Rs. For detection of Fc\u03b3RIIb (CD32B), a unique anti\u2010Fc\u03b3RIIb antibody (2B6\u2013fluorescein isothiocyanate [FITC]) was used. The capacity for antigen uptake by DCs was studied by assessing the uptake of FITC\u2010labeled ICs. Levels of cytokine production by DCs were measured during lipopolysaccharide\u2010mediated cell activation in the presence and absence of ICs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although no role of the <jats:italic>FCGR2B<\/jats:italic> variant in RA susceptibility was demonstrated, this variant was associated with a nearly doubled rate of radiologic joint damage during the first 6 years of RA. Multiple regression analysis showed that <jats:italic>FCGR2B<\/jats:italic> was by far the strongest predictor of joint damage identified to date. DCs from patients carrying this variant failed to display the inhibitory phenotype normally observed upon IC\u2010mediated triggering of inflammation and displayed diminished Fc\u03b3RII\u2010mediated antigen uptake compared with wild\u2010type DCs. However, the levels of Fc\u03b3Rs were not affected, suggesting that the <jats:italic>FCGR2B<\/jats:italic> variant alters the function rather than regulation of proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to show that a single genetic variant, the <jats:italic>FCGR2B<\/jats:italic> 695T&gt;C polymorphism, is a critical determinant of disease severity in RA and radically changes DC behavior. Our results underscore the key role of DCs in the progression of RA and reveal Fc\u03b3RIIb as an important potential therapeutic target in RA and other autoimmune conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22275","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T23:31:44Z","timestamp":1164756704000},"page":"3828-3837","source":"Crossref","is-referenced-by-count":49,"title":["The functional variant of the inhibitory Fc\u03b3 receptor IIb (CD32B) is associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis"],"prefix":"10.1002","volume":"54","author":[{"given":"Timothy R. D. 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