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Open AccessArticle

The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament

1
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
2
Department of Medicine, University Hospital “Príncipe de Asturias”, University of Alcalá and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá de Henares, 28871 Madrid, Spain
3
Immune System Diseases-Rheumatology Service, University Hospital “Príncipe de Asturias”, Alcalá de Henares, 28871 Madrid, Spain
4
Division of Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA 30322, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 871; https://doi.org/10.3390/cells8080871
Received: 15 June 2019 / Revised: 17 July 2019 / Accepted: 6 August 2019 / Published: 10 August 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Rheumatoid Arthritis)
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Abstract

Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their naïve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and Vβ TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-naïve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28− cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the Vβ TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-naïve RA patients with different patterns of alterations in MTX responders and non-responders. View Full-Text
Keywords: rheumatoid arthritis; CD4+ T lymphocytes; methotrexate; flow cytometry; TCR Vb rheumatoid arthritis; CD4+ T lymphocytes; methotrexate; flow cytometry; TCR Vb
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Monserrat, J.; Bohórquez, C.; Gómez Lahoz, A.M.; Movasat, A.; Pérez, A.; Ruíz, L.; Díaz, D.; Chara, L.; Sánchez, A.I.; Albarrán, F.; Sanz, I.; Álvarez-Mon, M. The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament. Cells 2019, 8, 871.

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