title: Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  Circulating plasmablasts/plasma cells and activated B and T cells are increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces differentiation of B cells into antibody-forming cells and of T cells into effector cells.
  
  
  OBJECTIVE
  To examine the hypothesis that blocking IL-6 would reverse some of the immune abnormalities present in SLE.
  
  
  METHODS
  Fifteen patients with SLE with mild-to moderate disease activity were treated with biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum immunoglobulin levels were compared at baseline and at weeks 6 and 12.
  
  
  RESULTS
  Tocilizumab decreased activated T and B cells, the frequency of CD27(high)CD38(high)IgD- plasmablasts/plasma cells and IgD-CD27+ post-switched memory B cells as well as IgG+ memory B cell, whereas it increased the frequency of IgD+CD27- antigen-inexperienced B cells. Among antigen-inexperienced IgD+CD27- B cells, CD38(low) mature naïve B cells increased significantly and CD38(Intermediate)CD5+ pre-naïve B cells showed a decreasing trend, whereas CD38(high)CD5+ transitional type 1 B cells did not change. Most of the changes occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3 serum levels decreased albeit within the normal range. The frequency of CD4+CD45RA+CCR7+ naïve T cells increased.
  
  
  CONCLUSIONS
  In vivo blockade of the IL-6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis by either blocking differentiation and/or trafficking in patients with SLE and leads to normalisation of the abnormal B and T cell subsets seen at baseline.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirota
authors.forename: Cheryl
authors.initials: C
authors.lastname: Yarboro
authors.forename: Randy
authors.initials: R
authors.lastname: Fischer
authors.forename: Tuyet-Hang
authors.initials: TH
authors.lastname: Pham
authors.forename: Peter
authors.initials: P
authors.lastname: Lipsky
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D010865:Pilot Projects; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019947:Receptors, Interleukin-6; C502936:tocilizumab