Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation

Anna M. Kip; Laurens J. Ceulemans; Inca H. R. Hundscheid; Emilio Canovai; Hermien Hartog; Rachel M. Brown; Olivier Corcos; Francisca Joly; Gert De Hertogh; Girish Gupte; Cornelis H. C. Dejong; Steven W. M. Olde Damink; Jacques Pirenne; Darius Mirza; Kaatje Lenaerts

doi:10.1097/TP.0000000000003257

Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation

Anna M. Kip, Laurens J. Ceulemans, Inca H. R. Hundscheid, Emilio Canovai, Hermien Hartog, Rachel M. Brown, Olivier Corcos, Francisca Joly, Gert De Hertogh, Girish Gupte, Cornelis H. C. Dejong, Steven W. M. Olde Damink, Jacques Pirenne, Darius Mirza, Kaatje Lenaerts^*

^*Corresponding author for this work

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Abstract

Background. 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. Methods. 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. Results. 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. Conclusions. 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.

Original language	English
Pages (from-to)	1952-1958
Number of pages	7
Journal	Transplantation
Volume	104
Issue number	9
DOIs	https://doi.org/10.1097/TP.0000000000003257
Publication status	Published - Sept 2020

Keywords

ANTIMICROBIAL PEPTIDES
GUT
SENSE

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10.1097/TP.0000000000003257

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Kip, A. M., Ceulemans, L. J., Hundscheid, I. H. R., Canovai, E., Hartog, H., Brown, R. M., Corcos, O., Joly, F., De Hertogh, G., Gupte, G., Dejong, C. H. C., Olde Damink, S. W. M., Pirenne, J., Mirza, D., & Lenaerts, K. (2020). Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation. Transplantation, 104(9), 1952-1958. https://doi.org/10.1097/TP.0000000000003257

@article{b8b2bf735f794f4caafdc0ae804baa38,

title = "Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation",

abstract = "Background. 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. Methods. 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. Results. 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. Conclusions. 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.",

keywords = "ANTIMICROBIAL PEPTIDES, GUT, SENSE",

author = "Kip, {Anna M.} and Ceulemans, {Laurens J.} and Hundscheid, {Inca H. R.} and Emilio Canovai and Hermien Hartog and Brown, {Rachel M.} and Olivier Corcos and Francisca Joly and {De Hertogh}, Gert and Girish Gupte and Dejong, {Cornelis H. C.} and {Olde Damink}, {Steven W. M.} and Jacques Pirenne and Darius Mirza and Kaatje Lenaerts",

note = "Funding Information: This research was supported by the Roche Organ Transplantation Research Foundation (ROTRF, grant ID 128921158). Publisher Copyright: {\textcopyright} 2020 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2020",

month = sep,

doi = "10.1097/TP.0000000000003257",

language = "English",

volume = "104",

pages = "1952--1958",

journal = "Transplantation",

issn = "0041-1337",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "9",

}

Kip, AM, Ceulemans, LJ, Hundscheid, IHR, Canovai, E, Hartog, H, Brown, RM, Corcos, O, Joly, F, De Hertogh, G, Gupte, G, Dejong, CHC, Olde Damink, SWM, Pirenne, J, Mirza, D & Lenaerts, K 2020, 'Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation', Transplantation, vol. 104, no. 9, pp. 1952-1958. https://doi.org/10.1097/TP.0000000000003257

TY - JOUR

T1 - Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation

AU - Kip, Anna M.

AU - Ceulemans, Laurens J.

AU - Hundscheid, Inca H. R.

AU - Canovai, Emilio

AU - Hartog, Hermien

AU - Brown, Rachel M.

AU - Corcos, Olivier

AU - Joly, Francisca

AU - De Hertogh, Gert

AU - Gupte, Girish

AU - Dejong, Cornelis H. C.

AU - Olde Damink, Steven W. M.

AU - Pirenne, Jacques

AU - Mirza, Darius

AU - Lenaerts, Kaatje

N1 - Funding Information: This research was supported by the Roche Organ Transplantation Research Foundation (ROTRF, grant ID 128921158). Publisher Copyright: © 2020 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2020/9

Y1 - 2020/9

N2 - Background. 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. Methods. 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. Results. 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. Conclusions. 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.

AB - Background. 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. Methods. 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. Results. 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. Conclusions. 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.

KW - ANTIMICROBIAL PEPTIDES

KW - GUT

KW - SENSE

U2 - 10.1097/TP.0000000000003257

DO - 10.1097/TP.0000000000003257

M3 - Article

C2 - 32265415

SN - 0041-1337

VL - 104

SP - 1952

EP - 1958

JO - Transplantation

JF - Transplantation

IS - 9

ER -