Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopenia
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
39965724
DOI
10.1016/j.clim.2025.110453
PII: S1521-6616(25)00028-2
Knihovny.cz E-resources
- Keywords
- Artificial thymic organoids (ATO), Congenital athymia, Diagnostic assays, Ex vivo T-lymphocyte differentiation, Hematopoietic cell transplantation (HCT), Newborn screening, Severe combined immunodeficiency (SCID), T-lymphocytopenia, Thymus transplantation,
- MeSH
- Cell Differentiation MeSH
- Child MeSH
- Immunophenotyping MeSH
- Infant MeSH
- Humans MeSH
- Lymphopenia * immunology MeSH
- Lymphopoiesis * genetics MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Primary Immunodeficiency Diseases therapy genetics immunology MeSH
- T-Lymphocytes * immunology MeSH
- Thymus Gland immunology MeSH
- Hematopoietic Stem Cell Transplantation * methods MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Persistent selective T-lymphocytopenia is found both in SCID and congenital athymia. Without molecular diagnosis, it is challenging to determine whether HCT or thymus transplantation ought to be performed. Ex vivo T-lymphopoiesis assays have been proposed to assist clinical decision-making for genetically undefined patients. We investigated 20 T-lymphocytopenic patients, including 13 patients awaiting first-line treatment and 7 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst developmental blocks in ex vivo T-lymphopoiesis indicated hematopoietic cell-intrinsic defects, successful T-lymphocyte differentiation required careful interpretation, in conjunction with clinical status, immunophenotyping, and genetic investigations. Of the 20 patients, 13 proceeded to treatment, with successful immune reconstitution observed in 4 of the 6 patients post-HCT and 4 of the 7 patients after thymus transplantation, the latter including two patients who had previously undergone HCT. Whilst further validation and standardization are required, we conclude that assessing ex vivo T-lymphopoiesis during the diagnostic pathway for genetically undefined T-lymphocytopenia improves patient outcomes by facilitating corrective treatment choice.
Allergy and Immunology Department The Royal Children's Hospital Melbourne Melbourne Australia
Center for Translational Immunology University Medical Center Utrecht; Utrecht Netherlands
Paediatric Immunology Department University Hospitals of Birmingham Birmingham United Kingdom
Paediatric Onco Haematology Unit Geneva University Hospital; Geneva Switzerland
References provided by Crossref.org
