Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopenia
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.
Authors
- Pere Soler‐Palacín (ORCID: https://orcid.org/0000-0002-0346-5570)
- Nufar Marcus (ORCID: https://orcid.org/0000-0002-9592-9255)
- Andrew Richard Gennery (ORCID: https://orcid.org/0000-0002-6218-1324)
- Irene Obiri-Yeboa
- Herbert Pichler (ORCID: https://orcid.org/0000-0001-5107-5123)
- Paul Torpiano (ORCID: https://orcid.org/0000-0002-6657-3579)
- Adrian J. Thrasher (ORCID: https://orcid.org/0000-0002-6097-6115)
- Fanette Bernard (ORCID: https://orcid.org/0000-0002-0220-6227)
- Maarja Soomann (ORCID: https://orcid.org/0000-0002-2237-5327)
- Sabrina Lizot (ORCID: https://orcid.org/0000-0002-5092-5779)
- Sophie Hambleton (ORCID: https://orcid.org/0000-0001-7954-3267)
- Theresa S. Cole (ORCID: https://orcid.org/0000-0002-8272-4074)
- Neil J. Sebire (ORCID: https://orcid.org/0000-0001-5348-9063)
- Alexandra Y. Kreins (ORCID: https://orcid.org/0000-0001-8748-5837)
- Antonio Marzollo (ORCID: https://orcid.org/0000-0003-2177-8500)
- Rajeev Rai (ORCID: https://orcid.org/0000-0003-4976-344X)
- Zainab Golwala (ORCID: https://orcid.org/0000-0002-8465-5746)
- Kaan Boztuǧ (ORCID: https://orcid.org/0000-0001-8387-9185)
- Zohreh Nademi (ORCID: https://orcid.org/0000-0002-3874-2646)
- Austen Worth (ORCID: https://orcid.org/0000-0001-6803-7385)
- Stuart Adams (ORCID: https://orcid.org/0000-0002-2650-2848)
- Anna Sellmer (ORCID: https://orcid.org/0000-0003-2464-5703)
- Juan Moisés Ocampo‐Godínez (ORCID: https://orcid.org/0000-0001-5666-4672)
- Ranjita Devi Moirangthem (ORCID: https://orcid.org/0000-0003-2182-0959)
- Susanne Kricke (ORCID: https://orcid.org/0000-0003-0791-2291)
- Matthew Buckland (ORCID: https://orcid.org/0000-0002-5646-4707)
- Victoria Bordon (ORCID: https://orcid.org/0000-0001-8446-0220)
- Mette Holm (ORCID: https://orcid.org/0000-0002-9159-4056)
- Joris van Montfrans
- Maaike Kusters (ORCID: https://orcid.org/0000-0001-7601-9822)
- Alexandrine Garrigue (ORCID: https://orcid.org/0000-0002-2660-3681)
- Kimberly Gilmour (ORCID: https://orcid.org/0000-0003-0285-3958)
- Stefan Nierkens (ORCID: https://orcid.org/0000-0003-3406-817X)
- Evey Howley
- Jana Pachlopnik Schmid (ORCID: https://orcid.org/0000-0002-6653-9047)
- Adam Klocperk (ORCID: https://orcid.org/0000-0002-1526-4557)
- Coco de Koning (ORCID: https://orcid.org/0000-0003-3992-8570)
- Isabelle André‐Schmutz (ORCID: https://orcid.org/0000-0002-3905-9910)
- Grace Evans
- Scott Hackett
- Arnold Awuah
- E. Graham Davies
- Marta Martin Corredera
- Helena Spiridou Goncalves (ORCID: https://orcid.org/0009-0002-6970-5618)
Institutions
- University of Padua (IT)
- Charles University (CZ)
- University Hospital in Motol (CZ)
Publication Details
- Journal
- Clinical Immunology
- Published
- 2025-02-16
- DOI
- https://doi.org/10.1016/j.clim.2025.110453
- Citations
- 1
- Primary Topic
- Immunodeficiency and Autoimmune Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Wellcome Trust
- Great Ormond Street Hospital Charity
- Medical Research Council