Dataset Information

Fc?RIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

ABSTRACT:

Objective

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.

Methods

Fc?RIIIa/CD16 expression on CD14(low) 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.

Results

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.

Conclusion

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.

SUBMITTER: Cooper DL

PROVIDER: S-EPMC3250404 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

Cooper Dawn L DL Martin Stephen G SG Robinson James I JI Mackie Sarah L SL Charles Christopher J CJ Nam Jackie J Isaacs John D JD Emery Paul P Morgan Ann W AW

PloS one 20120103 1

<h4>Objective</h4>The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy.<h4>Methods</h4>FcγRIIIa/CD16 expression on CD14(low) and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standi ...[more]

PMID: 22235253

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