title: Frequency of regulatory T cells is not affected by transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis.
abstract: OBJECTIVE
  Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristic regeneration pattern of B cell subpopulations has been reported. However, little is known about the impact of B-cell depletion on peripheral T cells in particular regulatory T cells.
  
  
  METHODS
  17 patients with RA having failed anti-TNF were treated with rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16, CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up to 12 months after rituximab. In addition, quantification of the soluble form of the HLA class I molecule HLA-G by ELISA has been performed.
  
  
  RESULTS
  Peripheral B cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+ lymphocytes showed no significant changes up to 1 year after B-cell depletion compared to before therapy. Only the relative frequency for CD3 and CD4 showed a significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive regulatory T cells remained constant. The percentage of HLA-G positive cells in the CD4+ or CD8+ population did not change significantly either. The amount of sHLA-G remained without significant changes.
  
  
  CONCLUSIONS
  Absolute T cell counts showed no significant changes after rituximab compared to the time point before therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++ phenotype as well as positive Foxp3 expression were numerically stable. Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G showed no significant changes.
authors.affiliation: University of Würzburg, Department of Medicine II, Rheumatology and Clinical Immunology, Germany. feuchtenbe_m@klinik.uni-wuerzburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Feuchtenberger
authors.forename: Sabine
authors.initials: S
authors.lastname: Müller
authors.forename: Petra
authors.initials: P
authors.lastname: Roll
authors.forename: Anne
authors.initials: A
authors.lastname: Waschbisch
authors.forename: Arne
authors.initials: A
authors.lastname: Schäfer
authors.forename: Christian
authors.initials: C
authors.lastname: Kneitz
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Tony