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Title: Differences in peripheral and tissue immune cell populations following haematopoietic stem cell transplantation in Crohn's disease patients
Author: Corraliza Márquez, Ana Maria
Ricart, Elena
López-García, Alicia
Masamunt, Maria Carme
Veny Alvarez-Ossorio, Marisol
Esteller, Manel
Mayorgas, Aida
Le Bourhis, Lionel
Allez, Matthieu
Planell Picola, Núria
Visvanathan, Sudha
Baum, Patrick
España, Carolina
Cabezón Cabello, Raquel
Benítez-Ribas, Daniel
Rovira Tarrats, Montserrat
Panés Díaz, Julià
Salas Martínez, Azucena
Keywords: Malaltia de Crohn
Cèl·lules mare
Crohn's disease
Stem cells
Issue Date: 26-Apr-2019
Publisher: Elsevier
Abstract: Background and aims: recent studies have shown the efficacy of autologous haematopoietic stem cell transplantation [HSCT] in severely refractory Crohn's disease [CD] patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. Methods: we followed a group of CD patients [n = 18] receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanisms driving efficacy, we monitored changes after HSCT in blood and intestine immune-cell composition. CD patients [n = 22] receiving anti-tumour necrosis factor [TNF]-α were included for comparison. Results: severe immune ablation followed by HSCT induced dramatic changes in both peripheral blood T and B cells in all patients regardless of the efficacy of the treatment. Endoscopic remission at week 52 following HSCT was associated with significant intestinal transcriptional changes. A comparison of the remission signature with that of anti-TNFα identified both common and unique genes in the HSCT-induced response. Based on deconvolution analysis of intestinal biopsy transcriptome data, we show that response to HSCT, but not to anti-TNFα, is associated with an expansion of naïve B-cells, as seen in blood, and a decrease in the memory resting T-cell content. As expected, endoscopic remission, in response to both HSCT and anti-TNFα, led to a significant reduction in intestinal neutrophil and M1 macrophage content. Conclusions: peripheral blood immune remodelling after HSCT does not predict efficacy. In contrast, a profound intestinal T-cell depletion that is maintained long after transplant is associated with mucosal healing following HSCT, but not anti-TNFα.
Note: Versió postprint del document publicat a:
It is part of: Journal of Crohn's and Colitis, 2019, vol. 13, num. 5, p. 634-647
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ISSN: 1873-9946
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Ciències Fisiològiques)

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