The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament
Jorge Monserrat,
Cristina Bohórquez,
Ana María Gómez Lahoz,
Atusa Movasat,
Ana Pérez,
Lucía Ruíz,
David Díaz,
Luis Chara,
Ana Isabel Sánchez,
Fernando Albarrán,
Ignacio Sanz,
Melchor Álvarez-Mon
Affiliations
Jorge Monserrat
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Cristina Bohórquez
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
Ana María Gómez Lahoz
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Atusa Movasat
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
Ana Pérez
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
Lucía Ruíz
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
David Díaz
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Luis Chara
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Ana Isabel Sánchez
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
Fernando Albarrán
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
Ignacio Sanz
Division of Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA 30322, USA
Melchor Álvarez-Mon
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain
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.
