title: Differential effects of biological DMARDs on peripheral immune cell phenotypes in patients with rheumatoid arthritis.
abstract: The aim of this study was to assess the therapeutic effects of biological DMARDs (bDMARDs) on the diversity of immune cell phenotypes in peripheral blood of patients with RA.
  
  
  
  Peripheral immune cell phenotypes were determined in 108 RA patients who were non-responsive to conventional DMARDs and 33 healthy control subjects by eight-colour flow cytometry. We also examined the correlation between the phenotypes and clinical findings and assessed the effects of 24-week treatment with bDMARDs.
  
  
  
  The proportions of T follicular helper (Tfh) cells, IgD- CD27- double negative B cells and plasmacytoid dendritic cells (pDCs) were higher in patients with active RA than in healthy control. The percentages of memory T cells, Th17 and Tfh cells correlated with autoantibody titres, whereas that of plasmablasts correlated with disease activity scores. Treatment with TNF inhibitors reduced the proportion of pDCs, while tocilizumab reduced the proportion of double-negative B cells but increased naïve and activated Treg cells. Abatacept treatment resulted in marked decrease in the proportion of activated Tfh but slightly reduced Th17 and Treg cells. The proportion of Tfh cells was an independent and significant predictor of the response to abatacept therapy.
  
  
  
  Molecular targeted therapies induced different changes in different immune cell phenotypes. Among the phenotypes, Tfh cells seem a potential target for abatacept. Immunophenotypic analysis might be useful for prediction of the response to bDMARDs.
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yunoue
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Iwata
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Miyagawa
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hirata
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakano
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000068879:Adalimumab / Q000627:therapeutic use; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D000068582:Certolizumab Pegol / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D016130:Immunophenotyping; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept; D000068582:Certolizumab Pegol
keywords: T follicular helper cells; biologic DMARDs; immunophenotype; plasmablasts; rheumatoid arthritis