Clinical application of immune repertoire sequencing in solid organ transplant

BackgroundMeasurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to pr...

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Main Authors: Paaksum Wong, Davide P. Cina, Karen R. Sherwood, Franz Fenninger, Ruth Sapir-Pichhadze, Constantin Polychronakos, James Lan, Paul A. Keown
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100479/full
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author Paaksum Wong
Davide P. Cina
Karen R. Sherwood
Karen R. Sherwood
Franz Fenninger
Franz Fenninger
Ruth Sapir-Pichhadze
Ruth Sapir-Pichhadze
Constantin Polychronakos
James Lan
James Lan
Paul A. Keown
Paul A. Keown
author_facet Paaksum Wong
Davide P. Cina
Karen R. Sherwood
Karen R. Sherwood
Franz Fenninger
Franz Fenninger
Ruth Sapir-Pichhadze
Ruth Sapir-Pichhadze
Constantin Polychronakos
James Lan
James Lan
Paul A. Keown
Paul A. Keown
author_sort Paaksum Wong
collection DOAJ
description BackgroundMeasurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance.ObjectiveWe performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring.MethodsWe searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation. Manual filtering of the search results was performed based on relevancy and predefined inclusion criteria. Data were extracted based on study and methodology characteristics.ResultsOur initial search yielded 1933 articles of which 37 met the inclusion criteria; 16 of these were kidney transplant studies (43%) and 21 were other or general transplantation studies (57%). The predominant method for repertoire characterization was sequencing the CDR3 region of the TCR β chain. Repertoires of transplant recipients were found to have decreased diversity in both rejectors and non-rejectors when compared to healthy controls. Rejectors and those with opportunistic infections were more likely to have clonal expansion in T or B cell populations. Mixed lymphocyte culture followed by TCR sequencing was used in 6 studies to define an alloreactive repertoire and in specialized transplant settings to track tolerance.ConclusionMethodological approaches to immune repertoire sequencing are becoming established and offer considerable potential as a novel clinical tool for pre- and post-transplant immune monitoring.
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spelling doaj.art-9641b2ef54fb4d38998a894ab99936242023-02-14T18:29:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11004791100479Clinical application of immune repertoire sequencing in solid organ transplantPaaksum Wong0Davide P. Cina1Karen R. Sherwood2Karen R. Sherwood3Franz Fenninger4Franz Fenninger5Ruth Sapir-Pichhadze6Ruth Sapir-Pichhadze7Constantin Polychronakos8James Lan9James Lan10Paul A. Keown11Paul A. Keown12Department of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Urologic Sciences, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, Division of Nephrology, McGill University, Montreal, QC, CanadaDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, CanadaDepartment of Pediatrics, The Research Institute of the McGill University Health Centre and the Montreal Children’s Hospital, Montreal, QC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaBackgroundMeasurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance.ObjectiveWe performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring.MethodsWe searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation. Manual filtering of the search results was performed based on relevancy and predefined inclusion criteria. Data were extracted based on study and methodology characteristics.ResultsOur initial search yielded 1933 articles of which 37 met the inclusion criteria; 16 of these were kidney transplant studies (43%) and 21 were other or general transplantation studies (57%). The predominant method for repertoire characterization was sequencing the CDR3 region of the TCR β chain. Repertoires of transplant recipients were found to have decreased diversity in both rejectors and non-rejectors when compared to healthy controls. Rejectors and those with opportunistic infections were more likely to have clonal expansion in T or B cell populations. Mixed lymphocyte culture followed by TCR sequencing was used in 6 studies to define an alloreactive repertoire and in specialized transplant settings to track tolerance.ConclusionMethodological approaches to immune repertoire sequencing are becoming established and offer considerable potential as a novel clinical tool for pre- and post-transplant immune monitoring.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100479/fullsolid organ transplantalloimmunitylymphocyte receptor sequencingB cell receptor (BCR)T cell receptor (TCR)
spellingShingle Paaksum Wong
Davide P. Cina
Karen R. Sherwood
Karen R. Sherwood
Franz Fenninger
Franz Fenninger
Ruth Sapir-Pichhadze
Ruth Sapir-Pichhadze
Constantin Polychronakos
James Lan
James Lan
Paul A. Keown
Paul A. Keown
Clinical application of immune repertoire sequencing in solid organ transplant
Frontiers in Immunology
solid organ transplant
alloimmunity
lymphocyte receptor sequencing
B cell receptor (BCR)
T cell receptor (TCR)
title Clinical application of immune repertoire sequencing in solid organ transplant
title_full Clinical application of immune repertoire sequencing in solid organ transplant
title_fullStr Clinical application of immune repertoire sequencing in solid organ transplant
title_full_unstemmed Clinical application of immune repertoire sequencing in solid organ transplant
title_short Clinical application of immune repertoire sequencing in solid organ transplant
title_sort clinical application of immune repertoire sequencing in solid organ transplant
topic solid organ transplant
alloimmunity
lymphocyte receptor sequencing
B cell receptor (BCR)
T cell receptor (TCR)
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100479/full
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