期刊
JOURNAL OF CROHNS & COLITIS
卷 13, 期 5, 页码 634-647出版社
OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjy203
关键词
Crohn's disease; autologous haematopoietic stem cell transplantation; anti-TNF alpha
资金
- Leona and Harry Helmsley Charitable Trust [2015PG-IBD005]
- Ministerio de Economia y Competitividad, Spain [SAF2015-66379-R]
- Instituto de Salud Carlos III
- Boehringer Ingelheim
- MSD
- Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas [CIBERehd]
- [PI17/00513]
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]-alpha 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-TNF alpha 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-TNF alpha, is associated with an expansion of naive 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-TNF alpha, 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-TNF alpha.
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