1. The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis
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David Díaz, Luis Chara, Miguel Ángel Sánchez, Ana Fernández Pérez, Melchor Alvarez-Mon, Fernando Albarrán, Ángel Asúnsolo del Barco, Jorge Monserrat, Julio Chevarria, Alfredo Prieto, Ana Isabel Turrión, Ignacio Sanz, Eduardo Cuende, Ana Sánchez-Atrio, and Antonio de la Hera
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Male ,musculoskeletal diseases ,CD14 ,CX3C Chemokine Receptor 1 ,chemical and pharmacologic phenomena ,Cell Count ,Monocyte ,Monocytes ,General Biochemistry, Genetics and Molecular Biology ,Arthritis, Rheumatoid ,immune system diseases ,Antigens, CD ,Cell Movement ,medicine ,Humans ,Distribution (pharmacology) ,Rheumatoid arthritis ,Demography ,Medicine(all) ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Case-control study ,virus diseases ,hemic and immune systems ,Biomarker ,General Medicine ,Middle Aged ,medicine.disease ,ANTIGENS CD ,biological factors ,Methotrexate ,Treatment Outcome ,medicine.anatomical_structure ,ROC Curve ,Case-Control Studies ,Immunology ,Clinical response ,Biomarker (medicine) ,Female ,Receptors, Chemokine ,business ,Biomarkers ,medicine.drug - 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. Electronic supplementary material The online version of this article (doi:10.1186/s12967-014-0375-y) contains supplementary material, which is available to authorized users.
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