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Immunology - Physiology - Rheumatology

Fc?RIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy
Published: Tuesday, January 03, 2012
Author: Dawn L. Cooper et al.

by Dawn L. Cooper, Stephen G. Martin, James I. Robinson, Sarah L. Mackie, Christopher J. Charles, Jackie Nam, YEAR Consortium, John D. Isaacs, Paul Emery, Ann W. Morgan


The expression of Fc?RIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether Fc?RIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy.


Fc?RIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. Fc?RIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined.


Increased Fc?RIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p?=?0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing Fc?RIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing Fc?RIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p?=?0.003) and was significantly increased in EULAR non-responders compared to moderate (p?=?0.01) or good responders (p?=?0.003). Fc?RIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers.


Increased Fc?RIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.