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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 Hematopoesi Limfòcits Crohn's disease Stem cells Hematopoiesis Lymphocytes |
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: https://doi.org/10.1093/ecco-jcc/jjy203 |
It is part of: | Journal of Crohn's and Colitis, 2019, vol. 13, num. 5, p. 634-647 |
URI: | http://hdl.handle.net/2445/155979 |
Related resource: | https://doi.org/10.1093/ecco-jcc/jjy203 |
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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