Treatment of rheumatoid arthritis patients with anti-TNF-α monoclonal antibody is accompanied by down-regulation of the activating Fcγ Receptor I on monocytes

Clinical and Experimental Rheumatology

F.P.J.G. Lafeber¹  J.G.J. van de Winkel¹  J.W.J. Bijlsma¹  J.A.G. van Roon¹  S. Wijngaarden¹ 

关键词: Rheumatoid arthritis;    monocytes;    Fcγ receptors;    anti-TNF.;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES:To study the effect of anti-TNF-α therapy on activating IgG Fc receptor (Fc&ggr;R) expression on monocytes of RA patients in relation to changes in disease activity.METHODS:RA patients were treated with anti-TNF-α mAb (infliximab). At baseline, 2 and 14 weeks after the start of anti-TNF-α treatment, Fc&ggr;R expression levels on circulating monocytes were evaluated. Changes in expression were correlated to changes in disease parameters. To study the direct effects of TNF-α blockade on monocytic Fc&ggr;R expression levels, monocytes were isolated and cultured with anti-TNF-α mAb. The effects were compared with those induced by TNF-α. RESULTS:Two weeks after the start of anti-TNF-α mAb therapy, monocytic Fc&ggr;RI expression levels were decreased, whereas Fc&ggr;RIIa and IIIa expression levels were unchanged. At 14 weeks, 8 weeks after the last gift of anti-TNF-α mAb, Fc&ggr;RI expression levels returned to baseline levels. Fc&ggr;RIIa and IIIa expression levels remained unchanged. The change in Fc&ggr;RI correlated with changes in CRP and ESR levels. In vitro, anti-TNF-α mAb treatment did not alter expression of Fc&ggr;RI on monocytes, but increased Fc&ggr;RIIa and IIIa. TNF-α down-regulated all activating Fc&ggr;Rs, mainly Fc&ggr;RIIa and IIIa, but also the inhibitory Fc&ggr;RIIb. CONCLUSIONS:Anti-TNF-α mAb treatment of RA patients is accompanied by down-regulation of Fc&ggr;RI expression levels on monocytes. This is likely an indirect effect of TNF-α blockade on disease activity, since in vitro anti-TNF-α mAb does not directly change Fc&ggr;RI expression on monocytes. In contrast, TNF-α down-regulated all activating Fc&ggr;Rs. Thus, blocking TNF-α may relieve the negative feedback mechanism of TNF-α as down-regulator of Fc&ggr;Rs. Strategies to reduce activating Fc&ggr;Rs may have additional value in the treatment of RA patients with TNF-α blockade by diminishing immune complex-mediated activation of monocytes/macrophages.

【 授权许可】

Unknown