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Open Access Research article

Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis

Luis Chara1, Ana Sánchez-Atrio2, Ana Pérez2, Eduardo Cuende2, Fernando Albarrán2, Ana Turrión2, Julio Chevarria1, Miguel A Sánchez1, Jorge Monserrat1, Antonio de la Hera1, Alfredo Prieto1, Ignacio Sanz3, David Diaz1 and Melchor Alvarez-Mon12*

Author Affiliations

1 Department of Medicine, University of Alcalá, N-II km 33, Alcala de Henares 28871, Spain

2 Immune System Diseases and Oncology Service, University Hospital "Príncipe de Asturias", N-II km 33, Alcala de Henares 28871, Spain

3 Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA

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Arthritis Research & Therapy 2012, 14:R175  doi:10.1186/ar3928

Published: 27 July 2012

Abstract

Introduction

The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFα) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment.

Methods

This prospective work investigated the number of circulating monocytes, and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNFα treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control.

Results

Non-responder patients with RA show an increased number of monocytes and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNFα treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders.

Conclusions

The absolute number of circulating monocytes and of their CD14+highCD16-, CD14+highCD16+ and CD14+lowCD16+ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.