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

• Published in: Cells (Basel, Switzerland) Switzerland), 2019-08, Vol.8 (8), p.871
• Main Authors: Monserrat, Jorge, Bohórquez, Cristina, Gómez Lahoz, Ana María, Movasat, Atusa, Pérez, Ana, Ruíz, Lucía, Díaz, David, Chara, Luis, Sánchez, Ana Isabel, Albarrán, Fernando, Sanz, Ignacio, Álvarez-Mon, Melchor
• Format: Article
• Language: English
• Subjects: Adult; Antigens; Antirheumatic Agents - pharmacology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoimmune diseases; CD28 antigen; CD4 antigen; CD4+ T lymphocytes; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - pathology; Cytokines; Disease; Drugs; Female; Flow cytometry; Humans; Immune system; Lymphocytes; Lymphocytes T; Male; Memory cells; Methotrexate; Methotrexate - pharmacology; Microscopy; Middle Aged; Patients; Quality of life; Rheumatoid arthritis; Rheumatology; T cell receptors; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - pathology; TCR Vb
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8080871

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 (T ), central memory (T ), effector memory (T ) and effector (T ) 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+ T , T , T and T lymphocyte subsets, and of total CD4+CD28- cells and of the T subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+T 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.