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Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus
  1. Yuko Shirota1,2,
  2. Cheryl Yarboro1,
  3. Randy Fischer3,
  4. Tuyet-Hang Pham1,
  5. Peter Lipsky4,
  6. Gabor G Illei1,2
  1. 1Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Sjögren's Syndrome Clinic, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
  3. 3Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  4. 4Charlottesville, Virginia, USA
  1. Correspondence to Dr Gabor G Illei, Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Room 1N 110, Bethesda, Maryland 20892, USA; illeig{at}mail.nih.gov

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 CD27highCD38highIgD− 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, CD38low mature naïve B cells increased significantly and CD38IntermediateCD5+ pre-naïve B cells showed a decreasing trend, whereas CD38highCD5+ 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.

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