PMID- 35095830
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20230917
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell 
      Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach 
      When Facing a Systemic Viral Infection.
PG  - 721917
LID - 10.3389/fimmu.2021.721917 [doi]
LID - 721917
AB  - 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.
CI  - Copyright (c) 2022 Chitty-Lopez, Duff, Vaughn, Trotter, Monforte, Lindsay, Haddad, 
      Keller, Oshrine and Leiding.
FAU - Chitty-Lopez, Maria
AU  - Chitty-Lopez M
AD  - Division of Pediatric Allergy and Immunology, University of South Florida, Tampa, 
      FL, United States.
FAU - Duff, Carla
AU  - Duff C
AD  - Division of Pediatric Allergy and Immunology, University of South Florida, Tampa, 
      FL, United States.
FAU - Vaughn, Gretchen
AU  - Vaughn G
AD  - Center for Cell and Gene Therapy for Non-Malignant Conditions, Cancer and Blood 
      Disorders Institute at Johns Hopkins All Children's Hospital, St. Petersburg, FL, 
      United States.
FAU - Trotter, Jessica
AU  - Trotter J
AD  - Division of Pediatric Allergy and Immunology, University of South Florida, Tampa, 
      FL, United States.
FAU - Monforte, Hector
AU  - Monforte H
AD  - Department of Pathology, Johns Hopkins All Children's Hospital, St. Petersburg, 
      FL, United States.
AD  - Division of Allergy and Immunology, Department of Pediatrics, University of Texas 
      Medical Branch, Galveston, TX, United States.
FAU - Lindsay, David
AU  - Lindsay D
AD  - Division of Allergy and Immunology, Department of Pediatrics, University of Texas 
      Medical Branch, Galveston, TX, United States.
AD  - Division of Immuno-Allergy and Rheumatology, The Centre Hospitalier Universitaire 
      Sainte-Justine, Montreal, QC, Canada.
FAU - Haddad, Elie
AU  - Haddad E
AD  - Division of Immuno-Allergy and Rheumatology, The Centre Hospitalier Universitaire 
      Sainte-Justine, Montreal, QC, Canada.
AD  - Division of Allergy and Immunology, Children's National Hospital, Washington, DC, 
      United States.
FAU - Keller, Michael D
AU  - Keller MD
AD  - Division of Allergy and Immunology, Children's National Hospital, Washington, DC, 
      United States.
FAU - Oshrine, Benjamin R
AU  - Oshrine BR
AD  - Center for Cell and Gene Therapy for Non-Malignant Conditions, Cancer and Blood 
      Disorders Institute at Johns Hopkins All Children's Hospital, St. Petersburg, FL, 
      United States.
FAU - Leiding, Jennifer W
AU  - Leiding JW
AD  - Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins 
      University, Baltimore, MD, United States.
AD  - Infectious Diseases and Immunology Division. Arnold Palmer Hospital for Children, 
      Orlando, FL, United States.
LA  - eng
PT  - Case Reports
DEP - 20220114
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (TBX1 protein, human)
RN  - Thymic aplasia
SB  - IM
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/methods
MH  - Humans
MH  - Immunologic Deficiency Syndromes/*genetics/surgery
MH  - Infant, Newborn
MH  - Severe Combined Immunodeficiency/genetics/surgery
MH  - Siblings
MH  - T-Box Domain Proteins/*genetics
MH  - Thymus Gland/*abnormalities/surgery
PMC - PMC8794793
OTO - NOTNLM
OT  - TBX1 congenital athymia
OT  - adenoviremia
OT  - definitive treatment
OT  - hematopoietic-stem-cell-transplantation
OT  - newborn screening (NBS)
COIS- JL is an employee and share holder of bluebird bio. MC-L is an employee and share 
      holder of Rocket Pharmaceuticals. The remaining authors declare that the research 
      was conducted in the absence of any commercial or financial relationships that 
      could be construed as a potential conflict of interest.
EDAT- 2022/02/01 06:00
MHDA- 2022/02/22 06:00
PMCR- 2021/01/01
CRDT- 2022/01/31 05:56
PHST- 2021/06/07 00:00 [received]
PHST- 2021/11/19 00:00 [accepted]
PHST- 2022/01/31 05:56 [entrez]
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.721917 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jan 14;12:721917. doi: 10.3389/fimmu.2021.721917. eCollection 
      2021.