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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
Notes:	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.
Subject(s):	-Malaltia de Crohn -Cèl·lules mare -Hematopoesi -Limfòcits -Crohn's disease -Stem cells -Hematopoiesis -Lymphocytes
Rights:	cc-by-nc-nd (c) European Crohn's and Colitis Organisation (ECCO), 2019 http://creativecommons.org/licenses/by-nc-nd/3.0/es
Document type:	Article Article - Accepted version
Published by:	Elsevier
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