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This work was supported by the Leona and Harry Helmsley Charitable Trust grant 2015PG-IBD005, by grant SAF2015-66379-R to AS and JP from the Ministerio de Economia y Competitividad, Spain, by Instituto de Salud Carlos III, by grant PI17/00513 to ER, by Boehringer Ingelheim and MSD. DB-R, NP and ME are supported by the Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas [CIBERehd].

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Differences in peripheral and tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients

Publicat a:Journal Of Crohns & Colitis. 13 (5): 634-647 - 2019-05-01 13(5), DOI: 10.1093/ecco-jcc/jjy203

Autors: Corraliza, Ana M; Ricart, Elena; Lopez-Garcia, Alicia; Carme Masamunt, Maria; Veny, Marisol; Esteller, Miriam; Mayorgas, Aida; Le Bourhis, Lionel; Allez, Matthieu; Planell, Nuria; Visvanathan, Sudha; Baum, Patrick; Espana, Carolina; Cabezon-Cabello, Raquel; Benitez-Ribas, Daniel; Rovira, Montserrat; Panes, Julian; Salas, Azucena

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Recent studies show the efficacy of autologous hematopoietic 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.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-tumor necrosis factor (TNF)- were included for comparisons.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-TNF identified both common and unique genes in the HSCT-induced response. Based on deconvolution analysis of intestinal biopsies transcriptome data, we show that response to HSCT, but not to anti-TNF, 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, both in response to HSCT or anti-TNF, led to a significant reduction in intestinal neutrophil and M1 macrophage content.Peripheral blood immune remodeling 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-TNF.

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