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

Objectives: To study the effect of anti-TNF-α therapy on activating IgG Fc receptor (FcγR) 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, FcγR 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 FcγR 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 FcγRI expression levels were decreased, whereas FcγRIIa and IIIa expression levels were unchanged. At 14 weeks, 8 weeks after the last gift of anti-TNF-α mAb, FcγRI expression levels returned to baseline levels. FcγRIIa and IIIa expression levels remained unchanged. The change in FcγRI correlated with changes in CRP and ESR levels. In vitro, anti-TNF-α mAb treatment did not alter expression of FcγRI on monocytes, but increased FcγRIIa and IIIa. TNF-α down-regulated all activating FcγRs, mainly FcγRIIa and IIIa, but also the inhibitory FcγRIIb. Conclusion: Anti-TNF-α mAb treatment of RA patients is accompanied by down-regulation of FcγRI 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 FcγRI expression on monocytes. In contrast, TNF-α down-regulated all activating FcγRs. Thus, blocking TNF-α may relieve the negative feedback mechanism of TNF-α as down-regulator of FcγRs. Strategies to reduce activating FcγRs may have additional value in the treatment of RA patients with TNF-α blockade by diminishing immune complex-mediated activation of monocytes/macrophages. © Copyright Clinical and Experimental Rheumatology 2008.