Corraliza Márquez, Ana MariaRicart, ElenaLópez-García, AliciaMasamunt, Maria CarmeVeny Alvarez-Ossorio, MarisolEsteller, ManelMayorgas, AidaLe Bourhis, LionelAllez, MatthieuPlanell Picola, NúriaVisvanathan, SudhaBaum, PatrickEspaña, CarolinaCabezón Cabello, RaquelBenítez-Ribas, DanielRovira Tarrats, MontserratPanés Díaz, JuliàSalas Martínez, Azucena2020-04-202020-04-262019-04-261873-9946https://hdl.handle.net/2445/155979Background 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.14 p.application/pdfengcc-by-nc-nd (c) European Crohn's and Colitis Organisation (ECCO), 2019http://creativecommons.org/licenses/by-nc-nd/3.0/esMalaltia de CrohnCèl·lules mareHematopoesiLimfòcitsCrohn's diseaseStem cellsHematopoiesisLymphocytesinfo:eu-repo/semantics/article6954042020-04-20info:eu-repo/semantics/openAccess30521002