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Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection

Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-b...

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Autores principales: Chitty-Lopez, Maria, Duff, Carla, Vaughn, Gretchen, Trotter, Jessica, Monforte, Hector, Lindsay, David, Haddad, Elie, Keller, Michael D., Oshrine, Benjamin R., Leiding, Jennifer W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794793/
https://www.ncbi.nlm.nih.gov/pubmed/35095830
http://dx.doi.org/10.3389/fimmu.2021.721917
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author Chitty-Lopez, Maria
Duff, Carla
Vaughn, Gretchen
Trotter, Jessica
Monforte, Hector
Lindsay, David
Haddad, Elie
Keller, Michael D.
Oshrine, Benjamin R.
Leiding, Jennifer W.
author_facet Chitty-Lopez, Maria
Duff, Carla
Vaughn, Gretchen
Trotter, Jessica
Monforte, Hector
Lindsay, David
Haddad, Elie
Keller, Michael D.
Oshrine, Benjamin R.
Leiding, Jennifer W.
author_sort Chitty-Lopez, Maria
collection PubMed
description Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.
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spelling pubmed-87947932022-01-29 Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection Chitty-Lopez, Maria Duff, Carla Vaughn, Gretchen Trotter, Jessica Monforte, Hector Lindsay, David Haddad, Elie Keller, Michael D. Oshrine, Benjamin R. Leiding, Jennifer W. Front Immunol Immunology Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections. Frontiers Media S.A. 2022-01-14 /pmc/articles/PMC8794793/ /pubmed/35095830 http://dx.doi.org/10.3389/fimmu.2021.721917 Text en Copyright © 2022 Chitty-Lopez, Duff, Vaughn, Trotter, Monforte, Lindsay, Haddad, Keller, Oshrine and Leiding https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chitty-Lopez, Maria
Duff, Carla
Vaughn, Gretchen
Trotter, Jessica
Monforte, Hector
Lindsay, David
Haddad, Elie
Keller, Michael D.
Oshrine, Benjamin R.
Leiding, Jennifer W.
Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title_full Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title_fullStr Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title_full_unstemmed Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title_short Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
title_sort case report: unmanipulated matched sibling donor hematopoietic cell transplantation in tbx1 congenital athymia: a lifesaving therapeutic approach when facing a systemic viral infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794793/
https://www.ncbi.nlm.nih.gov/pubmed/35095830
http://dx.doi.org/10.3389/fimmu.2021.721917
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