Shunsuke Fukuyo1, Shingo Nakayamada1, Shigeru Iwata1, Satoshi Kubo1, Kazuyoshi Saito1, Yoshiya Tanaka2. 1. The First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan. 2. The First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan. tanaka@med.uoeh-u.ac.jp.
Abstract
OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated. RESULTS: RA patients showed an increase in the proportion of CD28- cells among CD4+ cells, which was significantly high in patients who had not achieved remission after ABT therapy. The proportions of CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RA patients compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+ cells were significantly higher than those among CD4+CD28- cells. The proportion of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)-positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like (Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were significantly higher than those among CD4+CD28+ cells, and the proportion of these cells did not correlate with disease activity. After ABT therapy, the proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced. CONCLUSIONS: These results imply that CD4+ CD28+ Tfh-like cells could possibly be the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of treatment resistance.
OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RApatients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated. RESULTS:RApatients showed an increase in the proportion of CD28- cells among CD4+ cells, which was significantly high in patients who had not achieved remission after ABT therapy. The proportions of CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RApatients compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+ cells were significantly higher than those among CD4+CD28- cells. The proportion of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)-positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like (Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were significantly higher than those among CD4+CD28+ cells, and the proportion of these cells did not correlate with disease activity. After ABT therapy, the proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced. CONCLUSIONS: These results imply that CD4+ CD28+ Tfh-like cells could possibly be the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of treatment resistance.
Authors: Simon Glatigny; Barbara Höllbacher; Samantha J Motley; Cathy Tan; Christian Hundhausen; Jane H Buckner; Dawn Smilek; Samia J Khoury; Linna Ding; Tielin Qin; Jorge Pardo; Gerald T Nepom; Laurence A Turka; Kristina M Harris; Daniel J Campbell; Estelle Bettelli Journal: J Immunol Date: 2019-01-25 Impact factor: 5.422