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

• Type of Material: Article
• Authors: Jorge Monserrat, University of Alcalá; Cristina Bohorquez, University of Alcalá; Ana Maria Gomez Lahoz, University of Alcalá; Atusa Movasat, University of Alcalá; Ana Perez, University of Alcalá; Lucia Ruiz, University of Alcalá; David Diaz, University of Alcalá; Luis Chara, University of Alcalá; Ana Isabel Sanchez, University of Alcalá; Fernando Albarran, University of Alcalá; Ignacio Sanz, Emory University; Melchor Alvarez-Mon, University of Alcalá
• Language: English
• Date: 2019-08-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cells8080871
• Title of Journal or Parent Work: Cells
• ISSN: 2073-4409
• Volume: 8
• Issue: 8
• Grant/Funding Information: This work was partially supported by grants from the Fondo de Investigación de la Seguridad Social, Instituto de Salud Carlos III (PI18/01726), Spain and the Programa de Actividades de I+D de la Comunidad de Madrid en Biomedicina (B2017/BMD-3804), Madrid, Spain, and IRYCIS, Ciberehd isciii, Ministerio de Salud, Spain.
• Keywords: PERIPHERAL-BLOOD; Cell Biology; flow cytometry; Science & Technology; Life Sciences & Biomedicine; CD4+T lymphocytes; DIFFERENTIATION; methotrexate; RECEPTOR REPERTOIRE; TCR Vb; T-CELL SUBSETS; CLASSIFICATION; EFFECTOR; EXPRESSION; SYNOVIAL-FLUID; MEMORY; rheumatoid arthritis; AMERICAN-COLLEGE
• Research Categories: Biology, Cell; Health Sciences, Immunology

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.