Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children

Ugonna Offor; Paolo Hollis; Milos Ognjanovic; Gareth Perry; Abbas Khushnood; Heather Long; Andrew Gennery; Chris Bacon; Jacob Simmonds; Zdenka Reinhardt; Simon Bomken

doi:10.1136/bmjopen-2023-079582

Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children

Ugonna Offor^*, Paolo Hollis, Milos Ognjanovic, Gareth Perry, Abbas Khushnood, Heather Long, Andrew Gennery, Chris Bacon, Jacob Simmonds, Zdenka Reinhardt, Simon Bomken

^*Corresponding author for this work

Immunology and Immunotherapy

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

44 Downloads (Pure)

Abstract

Introduction: Paediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus-a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity-in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD.

Methods and analysis: Prospective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0-18 years), stratified into early (<1 year), late (>1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points.

Ethics and dissemination: Ethical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media.

Trial registration number: ISRCTN10096625.

Original language	English
Article number	e079582
Number of pages	7
Journal	BMJ open
Volume	13
Issue number	10
DOIs	https://doi.org/10.1136/bmjopen-2023-079582
Publication status	Published - 21 Oct 2023

Bibliographical note

Funding:
This study is funded by the Lymphoma Research Trust (N/A) and Cancer Research UK (PHSTU-Hist\100297). SB is funded by an MRC Clinician Scientist Fellowship (MR/S021590/1).

Keywords

Risk Factors
Paediatric oncology
Lymphoma
IMMUNOLOGY
Paediatric transplant surgery
Observational Study

Access to Document

10.1136/bmjopen-2023-079582Licence: Creative Commons: Attribution (CC BY)

OfforU2023ImmunologyFinal published version, 502 KBLicence: Creative Commons: Attribution (CC BY)

Fingerprint

Dive into the research topics of 'Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children'. Together they form a unique fingerprint.

Cite this

Offor, U., Hollis, P., Ognjanovic, M., Perry, G., Khushnood, A., Long, H., Gennery, A., Bacon, C., Simmonds, J., Reinhardt, Z., & Bomken, S. (2023). Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children. BMJ open, 13(10), Article e079582. https://doi.org/10.1136/bmjopen-2023-079582

@article{e06ad20c6dd948aea7dcd1181d517d9c,

title = "Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children",

abstract = "Introduction: Paediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus-a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity-in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD.Methods and analysis: Prospective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0-18 years), stratified into early (<1 year), late (>1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points.Ethics and dissemination: Ethical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media.Trial registration number: ISRCTN10096625.",

keywords = "Risk Factors, Paediatric oncology, Lymphoma, IMMUNOLOGY, Paediatric transplant surgery, Observational Study",

author = "Ugonna Offor and Paolo Hollis and Milos Ognjanovic and Gareth Perry and Abbas Khushnood and Heather Long and Andrew Gennery and Chris Bacon and Jacob Simmonds and Zdenka Reinhardt and Simon Bomken",

note = "Funding: This study is funded by the Lymphoma Research Trust (N/A) and Cancer Research UK (PHSTU-Hist\100297). SB is funded by an MRC Clinician Scientist Fellowship (MR/S021590/1).",

year = "2023",

month = oct,

day = "21",

doi = "10.1136/bmjopen-2023-079582",

language = "English",

volume = "13",

journal = "BMJ open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "10",

}

Offor, U, Hollis, P, Ognjanovic, M, Perry, G, Khushnood, A, Long, H, Gennery, A, Bacon, C, Simmonds, J, Reinhardt, Z & Bomken, S 2023, 'Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children', BMJ open, vol. 13, no. 10, e079582. https://doi.org/10.1136/bmjopen-2023-079582

Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children. / Offor, Ugonna; Hollis, Paolo; Ognjanovic, Milos et al.
In: BMJ open, Vol. 13, No. 10, e079582, 21.10.2023.

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

TY - JOUR

T1 - Immunology of THymectomy And childhood CArdiac transplant (ITHACA)

T2 - protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children

AU - Offor, Ugonna

AU - Hollis, Paolo

AU - Ognjanovic, Milos

AU - Perry, Gareth

AU - Khushnood, Abbas

AU - Long, Heather

AU - Gennery, Andrew

AU - Bacon, Chris

AU - Simmonds, Jacob

AU - Reinhardt, Zdenka

AU - Bomken, Simon

N1 - Funding: This study is funded by the Lymphoma Research Trust (N/A) and Cancer Research UK (PHSTU-Hist\100297). SB is funded by an MRC Clinician Scientist Fellowship (MR/S021590/1).

PY - 2023/10/21

Y1 - 2023/10/21

N2 - Introduction: Paediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus-a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity-in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD.Methods and analysis: Prospective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0-18 years), stratified into early (<1 year), late (>1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points.Ethics and dissemination: Ethical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media.Trial registration number: ISRCTN10096625.

AB - Introduction: Paediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus-a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity-in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD.Methods and analysis: Prospective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0-18 years), stratified into early (<1 year), late (>1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points.Ethics and dissemination: Ethical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media.Trial registration number: ISRCTN10096625.

KW - Risk Factors

KW - Paediatric oncology

KW - Lymphoma

KW - IMMUNOLOGY

KW - Paediatric transplant surgery

KW - Observational Study

U2 - 10.1136/bmjopen-2023-079582

DO - 10.1136/bmjopen-2023-079582

M3 - Article

SN - 2044-6055

VL - 13

JO - BMJ open

JF - BMJ open

IS - 10

M1 - e079582

ER -

Offor U, Hollis P, Ognjanovic M, Perry G, Khushnood A, Long H et al. Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children. BMJ open. 2023 Oct 21;13(10):e079582. doi: 10.1136/bmjopen-2023-079582