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FRI0095 Diversity of The Peripheral Immunological Phenotype after Biologic DMARD Therapy in Patients with Rheumatoid Arthritis
  1. S. Nakayamada,
  2. S. Kubo,
  3. M. Yoshikawa,
  4. Y. Miyazaki,
  5. N. Yunoue,
  6. S. Iwata,
  7. K. Nakano,
  8. K. Saito,
  9. Y. Tanaka
  1. The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

Abstract

Background In the pathogenesis of rheumatoid arthritis (RA), T cells can differentiate into functionally distinct subsets, leading to the persistent inflammation and immune abnormality associated with the interactive activation between B cells, monocytes and dendritic cells. However, little is known about pathological immune cell subsets targeted by biologic DMARDs (bDMARD) therapy.

Objectives The aim of this study was to assess the relationship between the phenotype of peripheral immune cells with clinical manifestations and responsiveness to bDMARD therapy in patients with RA.

Methods Peripheral blood mononuclear cells were obtained from 108 patients with bio-naïve RA and 26 healthy controls (HC). The study included 46 patients treated with TNF inhibitors such infliximab, etanercept and adalimumab, 40 patients treated with abatacept, and 22 patients treated with tocilizumab. The blood samples were taken at baseline and week 24 after treatment. The peripheral immune cell subset was defined based on comprehensive 8-color flow cytometric analysis for human immune system termed “the Human Immunology Project” by NIH and FOCIS, and the correlation with clinical characteristics and responsiveness to bDMARD therapies were evaluated.

Results The frequency of CD3+CD4+CD45RACCR7 effector memory, CD3+CD4+CD45RA+CCR7 effector T helper cells and CD4+CXCR5+ICOS+ T follicular helper (Tfh) cells was higher in patients with active RA than that in HC. The frequency of CD3+CD8+CD45RACCR7+ central memory cytotoxic T cells or CD3+CD4+CXCR3CCR6+ Th17 cells was correlated with RF titers and that of CD19+CD20CD27+CD38+ plasmablast was correlated with disease activity scores such as DAS28-ESR and SDAI. The proportion of Tfh cells and CD19+CD20+CD27IgD effector B cells made statistical clusters with that of plasmablast. All of bDMARDs markedly improved the disease activity scores after 24 week treatment. TNF inhibitors decreased CD3+CD4+CD45RA+CCR7+ naïve T cells but increased effector memory T cells and Th17 cells, and tocilizumab increased CD4+CCR4+CD25+CD127low T regulatory (Treg) cells and decreased effector B cells. However, abatacept characteristically decreased the proportions of T helper cell subsets which consisted of Tfh, Th17, and Treg cells and consequently the proportion of naïve T cells increased.

Conclusions These results indicated that the abnormal T cell differentiation correlated with autoantibody production while plasmablast did with disease activity of RA. In addition, the molecular targeted therapies may alter contradictory changes of T helper cell subsets, i.e. abatacept decreases activated Tfh, Th17 and Treg cells whereas TNF inhibitor increases Th17 cells and tocilizumab increases Treg cells. The peripheral immunophenotyping might be useful in evaluating the pathogenesis and in determining the therapeutic target of each patient.

Disclosure of Interest S. Nakayamada: None declared, S. Kubo: None declared, M. Yoshikawa: None declared, Y. Miyazaki: None declared, N. Yunoue: None declared, S. Iwata: None declared, K. Nakano: None declared, K. Saito: None declared, Y. Tanaka Grant/research support from: SantenMitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Consultant for: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD,

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