Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
Leuven Intestinal Failure and Transplantation (LIFT), Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium and Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
Transplantation. 2020 Sep;104(9):1952-1958. doi: 10.1097/TP.0000000000003257.
Ischemia-reperfusion injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PCs) are crucial for epithelial immune defense and highly vulnerable to ischemia-reperfusion injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis.
Endoscopic biopsies, collected according to center protocol and at rejection episodes, were retrospectively included (n = 28 ITx, n = 119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored.
We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared with T0. There was a tendency towards a larger decline in PC/crypt (P = 0.08) and lysozyme intensity (P = 0.08) in W1 in patients who later developed rejection compared with patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PCs were affected throughout rejection.
This study revealed a transient fall in PC numbers in the early post-ITx period but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx.
在肠移植（ITx）过程中，缺血再灌注损伤是不可避免的，并且在排斥反应的发展中起着关键作用。潘氏细胞（PCs）对上皮免疫防御至关重要，并且极易受到缺血再灌注损伤的影响。我们研究了 ITx 对再灌注后（T0）、随访期间和排斥反应期间 PC 的影响。此外，我们还研究了 PC 丢失是否与移植物稳态受损有关。
根据中心方案和排斥发作，回顾性纳入内镜活检（n = 28 例 ITx，n = 119 次活检）。活检采用 PC（溶菌酶）和凋亡的免疫组织化学共染色，并对 PC/隐窝和溶菌酶强度进行评分。
与 T0 相比，我们观察到 ITx 后第 1 周（W1）PC/隐窝和溶菌酶强度下降。与无排斥反应的患者相比，随后发生排斥反应的患者 W1 时 PC/隐窝（P = 0.08）和溶菌酶强度（P = 0.08）下降趋势更大。随访活检显示 PC 数量恢复，而溶菌酶强度仍然降低。这种持续存在的固有免疫缺陷可能导致肠道对感染的易感性众所周知。没有明确的证据表明 PC 在整个排斥反应过程中都受到影响。
本研究揭示了 ITx 后早期 PC 数量短暂下降，但 ITx 后溶菌酶强度永久降低。需要进一步研究来确定 ITx 后 PC 损伤的潜在临床影响。
