RT Journal Article
SR Electronic
T1 Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 118
OP 128
DO 10.1136/annrheumdis-2012-201310
VO 72
IS 1
A1 Yuko Shirota
A1 Cheryl Yarboro
A1 Randy Fischer
A1 Tuyet-Hang Pham
A1 Peter Lipsky
A1 Gabor G Illei
YR 2013
UL http://ard.bmj.com/content/72/1/118.abstract
AB 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.