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Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.
- Source :
-
Journal of Crohn's & colitis [J Crohns Colitis] 2019 Apr 26; Vol. 13 (5), pp. 634-647. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.<br /> (© European Crohn’s and Colitis Organisation (ECCO) 2018.)
Details
- Language :
- English
- ISSN :
- 1876-4479
- Volume :
- 13
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of Crohn's & colitis
- Publication Type :
- Academic Journal
- Accession number :
- 30521002
- Full Text :
- https://doi.org/10.1093/ecco-jcc/jjy203