Search in the Abstract Database

Search Abstracts 2012

* = Presenting author

P005. Restoration of Foxp3 regulatory T cells in blood correlates with clinical response to anti‑TNF therapy for IBD

Z. Li1, S. Vermeire1, D. Bullens2, M. Noman1, M. Ferrante1, P. Rutgeerts1, G. Van Assche1

1Catholic University of Leuven, UZ, Division of Gastroenterology, Leuven, Belgium; 2Catholic University of Leuven, UZ, Clinical Immunology Section, Leuven, Belgium

Background: It has been reported that Infliximab (IFX), a human-mouse chimeric monoclonal antibody, up-modulates circulating Foxp3 (+) T cells in patients with Inflammatory Bowel Disease (IBD), rheumatoid arthritis, psoriasis and Behçet's disease. Foxp3 expression is not restricted to regulatory T cells (Treg) in humans. CD45RA expression in combination with the strength of Foxp3 expression distinguishes resting and active regulatory T cells (rTreg and aTreg) from effector T cells (Teff). Our aim was to investigate which of these subsets is affected by anti‑TNF therapy.

Methods: In a cross sectional study, blood was taken from healthy controls (n = 39) and patients with IBD (n = 109, ulcerative colitis = 39, Crohn's disease = 70) before or during treatment with IFX (5 mg/kg induction and maintenance IV). The 3 subsets of Foxp3 T cells were assessed by staining with anti-CD4, anti-Foxp3 and anti-CD45RA, and analyzed by flow cytometry.

Results: 28 had active IBD before treatment, 65 were responders (RS) and 16 were non-responders (NRS)

  1. Both rTreg and aTreg in blood from patients with IBD before IFX therapy were significantly lower than in healthy controls (see Figure 1), confirming a deficiency of circulating rTreg and aTreg in IBD.
  2. During IFX therapy, rTregs in both RS and NRS were significantly higher than in IBD patients before therapy, and were in the normal range of HC. aTregs in RS were significantly higher compared to patients before therapy and to NRS, while this population remained lower in NRS than in HC.
  3. No significant differences in Foxp3 (+) Teff among HC and patients with IBD before or during IFX therapy were detected.

Legend: *p < 0.05; **p < 0.01; ***p < 0.001; NS: Not significant.

Conclusions: A deficiency of circulating Foxp3 (+) Treg in blood characterizes active IBD and the restoration of circulating activated Tregs correlates with the clinical response to anti‑TNF therapy. Further investigation of the pathways by which IFX up-modulates rTreg and aTreg will increase our understanding of the pathogenesis of IBD and the mechanism of action of anti‑TNF therapy.