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Title

Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation

Authors
Bettens, Florence
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Published in Leukemia. 2020, vol. 34, no. 5, p. 1422-1432
Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), immune reconstitution leads to the development of a new T-cell repertoire. Immune reconstitution could be influenced by events such as conditioning, infections, and graft versus host disease (GVHD). Factors influencing the TCR diversity are of great interest to fine-tune the strategy for donor selection and to optimize standard of care. In this work, immunosequencing of the TCR CDR3β region was carried out in a large cohort of 116 full chimeric recipients at 1 year post-HSCT and their respective donors prior to transplantation. The repertoire overlap before and after HSCT was minimal, supporting de novo reconstitution as a primary pathway at any age. Among the parameters investigated, increased patient and/or donor age as well as positive CMV serologic status reinforced by CMV infection/reactivation were the ones significantly associated with a reduced diversity at 1 year post-HSCT. CMV-specific T-cell clones were shown to influence the clonality of the repertoire alongside the expansion of limited numbers of non-CMV T-cell populations. Interestingly, at the exception of CMV infection/reactivation, TCR diversity was not predictive of GVHD, relapse, death, or infections post-HSCT.
Keywords AdolescentAdultAgedChildChild, PreschoolCohort StudiesCytomegalovirus/isolation & purificationCytomegalovirus Infections/diagnosis/etiology/geneticsFemaleFollow-Up StudiesGraft vs Host Disease/diagnosis/etiology/geneticsHematologic Neoplasms/pathology/therapyHematopoietic Stem Cell Transplantation/adverse effectsHumansInfantInfant, NewbornMaleMiddle AgedMutationPrognosisReceptors, Antigen, T-Cell/geneticsTissue Donors/supply & distributionTransplantation ConditioningTransplantation, HomologousVirus ActivationYoung Adult
Identifiers
PMID: 31772297
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Appendix (257 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: https://www.nature.com/articles/s41375-019-0654-y
Structures
Research groups Oncologie et hématologie pédiatrique (907)
Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
Project FNS: 310030_173237/1
Citation
(ISO format)
BUHLER, Stéphane et al. Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation. In: Leukemia, 2020, vol. 34, n° 5, p. 1422-1432. doi: 10.1038/s41375-019-0654-y https://archive-ouverte.unige.ch/unige:143931

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Deposited on : 2020-11-02

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