Li, Z. et al. Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab. Inflamm. Bowel Dis. 16, 1299-1310

Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium.
Inflammatory Bowel Diseases (Impact Factor: 4.46). 08/2010; 16(8):1299-310. DOI: 10.1002/ibd.21229
Source: PubMed


Immune therapies may act in inflammatory bowel diseases (IBD) by modulating regulatory T cells (Tregs). Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC).
Forty patients with active IBD (23 CD / 17 UC) were treated with IFX 5 mg/kg intravenously at weeks 0, 2, 6, and each 8 weeks thereafter. Blood samples were obtained before every infusion and T-lymphocyte subsets were characterized by flow cytometry. Foxp3 expression in intestinal biopsies from 43 patients with active IBD (19 CD / 24 UC) before and after IFX infusion and from 6 controls were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Plasma C-reactive protein (CRP), clinical response, and endoscopic healing data were collected in parallel.
IFX therapy resulted in a significant and sustained relative increase of CD4(+)CD25(+)Foxp3(+) Treg and of CD4(+)CD25(-)Foxp3(+) Treg cells in peripheral blood (both P < 0.0001 compared to baseline), particularly in responders (both P < 0.05 compared to nonresponders). The change in CRP over time inversely correlated with the increase of CD25(+)Foxp3(+) cells (P < 0.001, r = -0.39) and durable clinical response was associated with a sustained increase of circulating Foxp3(+) cells. Surprisingly, IFX therapy downregulated mucosal mRNA and protein expression of Foxp3 in UC and CD responders (both P < 0.001) but not in nonresponders.
IFX therapy has opposite effects in Foxp3(+) Treg cells in blood and gut mucosa, which suggests a redistribution of this important T-cell subset.

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Available from: Jan Ceuppens, Nov 13, 2014
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    • "In IBD patients, data on Tregs have been somewhat conflicting. Recent studies showed that anti-TNFí µí»¼ treatment increases Treg level in the peripheral blood of IBD patients [21] [22] [23], especially in clinical responders [22] [23]. However, this has not been confirmed by the study of Grundström et al. [24]. "
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    • "0.7 [0.5–3.1] CDAI 234 [194–256] 327 [312–374] HBI 9 [7] [8] [9] [10] 12 [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] "
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