The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis

• Type of Material: Article
• Authors: Luis Chara, University of Alcalá; Ana Sanchez-Atrio, University Hospital Príncipe de Asturias; Ana Perez, University Hospital Príncipe de Asturias; Eduardo Cuende, University Hospital Príncipe de Asturias; Fernando Albarran, University Hospital Príncipe de Asturias; Ana Turrion, University Hospital Príncipe de Asturias; Julio Chevarria, University Hospital Príncipe de Asturias; Angel Asunsolo del Barco, University of Alcalá; Miguel A Sanchez, University of Alcalá; Jorge Monserrat, University of Alcalá; Alfredo Prieto, University of Alcalá; Antonio de la Hera, University of Alcalá; Ignacio Sanz, Emory University; David Diaz, University of Alcalá; Melchor Alvarez-Mon, University of Alcalá
• Language: English
• Date: 2015-01-16
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Chara et al.; licensee BioMed Central.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12967-014-0375-y
• Title of Journal or Parent Work: Journal of Translational Medicine
• ISSN: 1479-5876
• Volume: 13
• Grant/Funding Information: This work was partially funded by grants from the Fondo de Investigación de la Seguridad Social (Spain), Consejeria de Educación, Comunidad de Madrid, MITIC-CM (S-2010/BMD-2502), and the Spanish Ministerio de Ciencia y Tecnología, Instituto de Salud Carlos III (PI051871, CIBERehd).
• Keywords: SUBSETS; Research & Experimental Medicine; RESPONSIVENESS; INFLAMMATION; DENDRITIC CELLS; Methotrexate; PERIPHERAL-BLOOD; Life Sciences & Biomedicine; BIOCHIP ARRAY TECHNOLOGY; HETEROGENEITY; MACROPHAGES; Monocyte; VALIDATION; Biomarker; Science & Technology; Clinical response; Rheumatoid arthritis; Medicine, Research & Experimental; CD14(+)CD16(+) MONOCYTES
• Research Categories: Health Sciences, Immunology

Abstract

Background: The aim of this work was to analyze the number and distribution of circulating monocytes, and of their CD14^+highCD16^-, CD14^+highCD16⁺ and CD14^+lowCD16⁺ subset cells, in treatment-naive patients with rheumatoid arthritis (RA), and to determine their value in predicting the clinical response to methotrexate (MTX) treatment. Methods: This prospective work investigated the number of circulating monocytes, and the numbers of CD14^+highCD16^-, CD14^+highCD16⁺ and CD14^+lowCD16⁺ subset cells, in 52 untreated patients with RA before MTX treatment, and at 3 and 6 months into treatment, using flow cytometry. Results: The absolute number of circulating monocytes, and the numbers of CD14^+highCD16^-, CD14^+highCD16⁺ and CD14^+lowCD16⁺ subset cells, were significantly higher in MTX non-responders than in responders and healthy controls before starting and throughout treatment. Responders showed normal numbers of monocytes, and of their subset cells, over the study period. The pre-treatment absolute number of circulating monocytes, and the numbers of CD14^+highCD16^- and CD14^+highCD16⁺ subset cells, were found to be predictive of the clinical response to MTX, with a sensitivity and specificity of >70% and >88%, respectively. Conclusions: Treatment-naive patients with RA showed an anomalous distribution of circulating monocyte subsets, and an anomalous number of cells in each subset. A higher pre-treatment number of circulating monocytes, and higher numbers of CD14^+highCD16^- and CD14^+highCD16⁺ subset cells, predict a reduced clinical response to MTX in untreated patients with RA.