Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series

TransplantLines Investigators; Naomi Karmi; Roy Oelen; Emilia Bigaeva; Sofie De Jong; Jan Willem Haveman; Frans Van Der Heide; Marcela A. Hermoso; Monique G.P. Van Der Wijst; Gursah Kats-Ugurlu; Rinse K. Weersma; Eleonora A.M. Festen; Werna T.C. Uniken Venema; Gerard Dijkstra

doi:10.1097/TP.0000000000005411

Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series

TransplantLines Investigators, Naomi Karmi, Roy Oelen, Emilia Bigaeva, Sofie De Jong, Jan Willem Haveman, Frans Van Der Heide, Marcela A. Hermoso, Monique G.P. Van Der Wijst, Gursah Kats-Ugurlu, Rinse K. Weersma, Eleonora A.M. Festen, Werna T.C. Uniken Venema^*, Gerard Dijkstra

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival is only 56%, possibly due to an imbalance in immunosuppression, aiming to prevent rejection while maintaining protection against pathogens. Studying the graft's mucosal cell populations and regulation of donor and recipient cells posttransplantation offers a unique opportunity to address this (im)balance leading to rejection.

METHODS: We performed single-cell mRNA sequencing of longitudinally sampled ileal graft biopsies from surgery up to 6 mo after transplantation, althrough the TransplantLines Biobank and Cohort Study to characterize the composition and function of donor and recipient cell populations.

RESULTS: A rapid influx of recipient immune cells was observed in the rejected transplant. Induction therapy using anti-thymocyte globulin did not achieve complete T-cell depletion. Instead, during moderate rejection, apoptotic pathways in epithelial cells preceded pathology-defined severe rejection, indicating potential prognostic information in the transcriptomic profiles.

CONCLUSIONS: This first longitudinal cellular-molecular study of the total ileal graft mucosa and recipient cells within, shows a variable clinical course and response to medication, which align with heterogeneous signatures before intestinal transplantation rejection.

Original language	English
Number of pages	10
Journal	Transplantation
DOIs	https://doi.org/10.1097/TP.0000000000005411
Publication status	E-pub ahead of print - 24-Apr-2025

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Insights in Cellular and Molecular Signatures of the Small Intestinal Graft PosttransplantationFinal publisher's version, 1.24 MBLicence: CC BY

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TransplantLines
Bakker, S. (Creator), Leuvenink, H. G. D. (Creator) & Porte, R. J. (Creator), University of Groningen, 2017
DOI: 10.34760/5f5b80abd0b30, http://www.transplantlines.umcg.nl
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TransplantLines Investigators, Karmi, N., Oelen, R., Bigaeva, E., De Jong, S., Haveman, J. W., Van Der Heide, F., Hermoso, M. A., Van Der Wijst, M. G. P., Kats-Ugurlu, G., Weersma, R. K., Festen, E. A. M., Uniken Venema, W. T. C., & Dijkstra, G. (2025). Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series. Transplantation. Advance online publication. https://doi.org/10.1097/TP.0000000000005411

@article{a9c2170eccf941e9be513385763dbf9e,

title = "Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series",

abstract = "BACKGROUND: Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival is only 56\%, possibly due to an imbalance in immunosuppression, aiming to prevent rejection while maintaining protection against pathogens. Studying the graft's mucosal cell populations and regulation of donor and recipient cells posttransplantation offers a unique opportunity to address this (im)balance leading to rejection.METHODS: We performed single-cell mRNA sequencing of longitudinally sampled ileal graft biopsies from surgery up to 6 mo after transplantation, althrough the TransplantLines Biobank and Cohort Study to characterize the composition and function of donor and recipient cell populations.RESULTS: A rapid influx of recipient immune cells was observed in the rejected transplant. Induction therapy using anti-thymocyte globulin did not achieve complete T-cell depletion. Instead, during moderate rejection, apoptotic pathways in epithelial cells preceded pathology-defined severe rejection, indicating potential prognostic information in the transcriptomic profiles.CONCLUSIONS: This first longitudinal cellular-molecular study of the total ileal graft mucosa and recipient cells within, shows a variable clinical course and response to medication, which align with heterogeneous signatures before intestinal transplantation rejection.",

author = "\{TransplantLines Investigators\} and Naomi Karmi and Roy Oelen and Emilia Bigaeva and \{De Jong\}, Sofie and Haveman, \{Jan Willem\} and \{Van Der Heide\}, Frans and Hermoso, \{Marcela A.\} and \{Van Der Wijst\}, \{Monique G.P.\} and Gursah Kats-Ugurlu and Weersma, \{Rinse K.\} and Festen, \{Eleonora A.M.\} and \{Uniken Venema\}, \{Werna T.C.\} and Gerard Dijkstra and C. Annema and Berger, \{S. P.\} and H. Blokzijl and Bodewes, \{F. A.J.A.\} and \{De Boer\}, \{M. T.\} and K. Damman and \{De Borst\}, \{M. H.\} and A. Diepstra and Douwes, \{R. M.\} and Doorenbos, \{C. S.E.\} and Eisenga, \{M. F.\} and Erasmus, \{M. E.\} and Gan, \{C. T.\} and \{Gomes Neto\}, \{A. W.\} and E. Hak and Hepkema, \{B. G.\} and F. Klont and Knobbe, \{T. J.\} and D. Kremer and Leuvenink, \{H. G.D.\} and \{De Meijer\}, \{V. E.\} and Niesters, \{H. G.M.\} and \{Van Pelt\}, \{L. J.\} and Pol, \{R. A.\} and Porte, \{R. J.\} and Ranchor, \{A. V.\} and Sanders, \{J. S.F.\} and Siebelink, \{M. J.\} and Slart, \{R. J.H.J.A.\} and Swarte, \{J. C.\} and Touw, \{D. J.\} and \{Van Den Heuvel\}, \{M. C.\} and \{Van Leer-Buter\}, C. and \{Van Londen\}, M. and \{Te Velde-Keyzer\}, \{C. A.\} and Verschuuren, \{E. A.M.\} and Vos, \{M. J.\}",

note = "Copyright {\textcopyright} 2025 The Author(s). Published by Wolters Kluwer Health, Inc.",

year = "2025",

month = apr,

day = "24",

doi = "10.1097/TP.0000000000005411",

language = "English",

journal = "Transplantation",

issn = "0041-1337",

publisher = "Lippincott Williams and Wilkins",

}

TransplantLines Investigators, Karmi, N , Oelen, R , Bigaeva, E , De Jong, S , Haveman, JW , Van Der Heide, F , Hermoso, MA , Van Der Wijst, MGP , Kats-Ugurlu, G , Weersma, RK , Festen, EAM , Uniken Venema, WTC & Dijkstra, G 2025, 'Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series', Transplantation. https://doi.org/10.1097/TP.0000000000005411

TY - JOUR

T1 - Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation

T2 - Successful, Recovered, and Rejected - A Case Series

AU - TransplantLines Investigators

AU - Karmi, Naomi

AU - Oelen, Roy

AU - Bigaeva, Emilia

AU - De Jong, Sofie

AU - Haveman, Jan Willem

AU - Van Der Heide, Frans

AU - Hermoso, Marcela A.

AU - Van Der Wijst, Monique G.P.

AU - Kats-Ugurlu, Gursah

AU - Weersma, Rinse K.

AU - Festen, Eleonora A.M.

AU - Uniken Venema, Werna T.C.

AU - Dijkstra, Gerard

AU - Annema, C.

AU - Berger, S. P.

AU - Blokzijl, H.

AU - Bodewes, F. A.J.A.

AU - De Boer, M. T.

AU - Damman, K.

AU - De Borst, M. H.

AU - Diepstra, A.

AU - Douwes, R. M.

AU - Doorenbos, C. S.E.

AU - Eisenga, M. F.

AU - Erasmus, M. E.

AU - Gan, C. T.

AU - Gomes Neto, A. W.

AU - Hak, E.

AU - Hepkema, B. G.

AU - Klont, F.

AU - Knobbe, T. J.

AU - Kremer, D.

AU - Leuvenink, H. G.D.

AU - De Meijer, V. E.

AU - Niesters, H. G.M.

AU - Van Pelt, L. J.

AU - Pol, R. A.

AU - Porte, R. J.

AU - Ranchor, A. V.

AU - Sanders, J. S.F.

AU - Siebelink, M. J.

AU - Slart, R. J.H.J.A.

AU - Swarte, J. C.

AU - Touw, D. J.

AU - Van Den Heuvel, M. C.

AU - Van Leer-Buter, C.

AU - Van Londen, M.

AU - Te Velde-Keyzer, C. A.

AU - Verschuuren, E. A.M.

AU - Vos, M. J.

PY - 2025/4/24

Y1 - 2025/4/24

N2 - BACKGROUND: Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival is only 56%, possibly due to an imbalance in immunosuppression, aiming to prevent rejection while maintaining protection against pathogens. Studying the graft's mucosal cell populations and regulation of donor and recipient cells posttransplantation offers a unique opportunity to address this (im)balance leading to rejection.METHODS: We performed single-cell mRNA sequencing of longitudinally sampled ileal graft biopsies from surgery up to 6 mo after transplantation, althrough the TransplantLines Biobank and Cohort Study to characterize the composition and function of donor and recipient cell populations.RESULTS: A rapid influx of recipient immune cells was observed in the rejected transplant. Induction therapy using anti-thymocyte globulin did not achieve complete T-cell depletion. Instead, during moderate rejection, apoptotic pathways in epithelial cells preceded pathology-defined severe rejection, indicating potential prognostic information in the transcriptomic profiles.CONCLUSIONS: This first longitudinal cellular-molecular study of the total ileal graft mucosa and recipient cells within, shows a variable clinical course and response to medication, which align with heterogeneous signatures before intestinal transplantation rejection.

AB - BACKGROUND: Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival is only 56%, possibly due to an imbalance in immunosuppression, aiming to prevent rejection while maintaining protection against pathogens. Studying the graft's mucosal cell populations and regulation of donor and recipient cells posttransplantation offers a unique opportunity to address this (im)balance leading to rejection.METHODS: We performed single-cell mRNA sequencing of longitudinally sampled ileal graft biopsies from surgery up to 6 mo after transplantation, althrough the TransplantLines Biobank and Cohort Study to characterize the composition and function of donor and recipient cell populations.RESULTS: A rapid influx of recipient immune cells was observed in the rejected transplant. Induction therapy using anti-thymocyte globulin did not achieve complete T-cell depletion. Instead, during moderate rejection, apoptotic pathways in epithelial cells preceded pathology-defined severe rejection, indicating potential prognostic information in the transcriptomic profiles.CONCLUSIONS: This first longitudinal cellular-molecular study of the total ileal graft mucosa and recipient cells within, shows a variable clinical course and response to medication, which align with heterogeneous signatures before intestinal transplantation rejection.

U2 - 10.1097/TP.0000000000005411

DO - 10.1097/TP.0000000000005411

M3 - Article

C2 - 40280178

SN - 0041-1337

JO - Transplantation

JF - Transplantation

ER -

Insights in Cellular and Molecular Signatures of the Small Intestinal Graft Posttransplantation: Successful, Recovered, and Rejected - A Case Series

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