Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia

Zainab M Golwala; Helena Spiridou Goncalves; Ranjita Devi Moirangthem; Grace Evans; Sabrina Lizot; Coco de Koning; Alexandrine Garrigue; Marta Martin Corredera; Juan Moises Ocampo-Godinez; Evey Howley; Susanne Kricke; Arnold Awuah; Irene Obiri-Yeboa; Rajeev Rai; Neil Sebire; Fanette Bernard; Victoria Bordon Cueto De Braem; Kaan Boztug; Theresa Cole; Andrew R Gennery; Scott Hackett; Sophie Hambleton; Mette Holm; Maaike A Kusters; Adam Klocperk; Antonio Marzollo; Nufar Marcus; Zohreh Nademi; Jana Pachlopnik Schmid; Herbert Pichler; Anna Sellmer; Pere Soler-Palacin; Maarja Soomann; Paul Torpiano; Joris van Montfrans; Stefan Nierkens; Stuart Adams; Matthew Buckland; Kimberly Gilmour; Austen Worth; Adrian J Thrasher; E Graham Davies; Isabelle André; Alexandra Y Kreins

doi:10.1016/j.clim.2025.110453

Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia

Zainab M Golwala, Helena Spiridou Goncalves, Ranjita Devi Moirangthem, Grace Evans, Sabrina Lizot, Coco de Koning, Alexandrine Garrigue, Marta Martin Corredera, Juan Moises Ocampo-Godinez, Evey Howley, Susanne Kricke, Arnold Awuah, Irene Obiri-Yeboa, Rajeev Rai, Neil Sebire, Fanette Bernard, Victoria Bordon Cueto De Braem, Kaan Boztug, Theresa Cole, Andrew R GenneryScott Hackett, Sophie Hambleton, Mette Holm, Maaike A Kusters, Adam Klocperk, Antonio Marzollo, Nufar Marcus, Zohreh Nademi, Jana Pachlopnik Schmid, Herbert Pichler, Anna Sellmer, Pere Soler-Palacin, Maarja Soomann, Paul Torpiano, Joris van Montfrans, Stefan Nierkens, Stuart Adams, Matthew Buckland, Kimberly Gilmour, Austen Worth, Adrian J Thrasher, E Graham Davies, Isabelle André, Alexandra Y Kreins

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	110453
Number of pages	13
Journal	Clinical Immunology
Volume	274
Early online date	16 Feb 2025
DOIs	https://doi.org/10.1016/j.clim.2025.110453
Publication status	E-pub ahead of print - 16 Feb 2025

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Golwala, Z. M., Goncalves, H. S., Moirangthem, R. D., Evans, G., Lizot, S., de Koning, C., Garrigue, A., Corredera, M. M., Ocampo-Godinez, J. M., Howley, E., Kricke, S., Awuah, A., Obiri-Yeboa, I., Rai, R., Sebire, N., Bernard, F., De Braem, V. B. C., Boztug, K., Cole, T., ... Kreins, A. Y. (2025). Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia. Clinical Immunology, 274, Article 110453. Advance online publication. https://doi.org/10.1016/j.clim.2025.110453

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title = "Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia",

abstract = "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.",

author = "Golwala, {Zainab M} and Goncalves, {Helena Spiridou} and Moirangthem, {Ranjita Devi} and Grace Evans and Sabrina Lizot and {de Koning}, Coco and Alexandrine Garrigue and Corredera, {Marta Martin} and Ocampo-Godinez, {Juan Moises} and Evey Howley and Susanne Kricke and Arnold Awuah and Irene Obiri-Yeboa and Rajeev Rai and Neil Sebire and Fanette Bernard and {De Braem}, {Victoria Bordon Cueto} and Kaan Boztug and Theresa Cole and Gennery, {Andrew R} and Scott Hackett and Sophie Hambleton and Mette Holm and Kusters, {Maaike A} and Adam Klocperk and Antonio Marzollo and Nufar Marcus and Zohreh Nademi and Schmid, {Jana Pachlopnik} and Herbert Pichler and Anna Sellmer and Pere Soler-Palacin and Maarja Soomann and Paul Torpiano and {van Montfrans}, Joris and Stefan Nierkens and Stuart Adams and Matthew Buckland and Kimberly Gilmour and Austen Worth and Thrasher, {Adrian J} and Davies, {E Graham} and Isabelle Andr{\'e} and Kreins, {Alexandra Y}",

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year = "2025",

month = feb,

day = "16",

doi = "10.1016/j.clim.2025.110453",

language = "English",

volume = "274",

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Golwala, ZM, Goncalves, HS, Moirangthem, RD, Evans, G, Lizot, S, de Koning, C, Garrigue, A, Corredera, MM, Ocampo-Godinez, JM, Howley, E, Kricke, S, Awuah, A, Obiri-Yeboa, I, Rai, R, Sebire, N, Bernard, F, De Braem, VBC, Boztug, K, Cole, T, Gennery, AR, Hackett, S, Hambleton, S, Holm, M, Kusters, MA, Klocperk, A, Marzollo, A, Marcus, N, Nademi, Z, Schmid, JP, Pichler, H, Sellmer, A, Soler-Palacin, P, Soomann, M, Torpiano, P, van Montfrans, J , Nierkens, S, Adams, S, Buckland, M, Gilmour, K, Worth, A, Thrasher, AJ, Davies, EG, André, I & Kreins, AY 2025, 'Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia', Clinical Immunology, vol. 274, 110453. https://doi.org/10.1016/j.clim.2025.110453

TY - JOUR

T1 - Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia

AU - Golwala, Zainab M

AU - Goncalves, Helena Spiridou

AU - Moirangthem, Ranjita Devi

AU - Evans, Grace

AU - Lizot, Sabrina

AU - de Koning, Coco

AU - Garrigue, Alexandrine

AU - Corredera, Marta Martin

AU - Ocampo-Godinez, Juan Moises

AU - Howley, Evey

AU - Kricke, Susanne

AU - Awuah, Arnold

AU - Obiri-Yeboa, Irene

AU - Rai, Rajeev

AU - Sebire, Neil

AU - Bernard, Fanette

AU - De Braem, Victoria Bordon Cueto

AU - Boztug, Kaan

AU - Cole, Theresa

AU - Gennery, Andrew R

AU - Hackett, Scott

AU - Hambleton, Sophie

AU - Holm, Mette

AU - Kusters, Maaike A

AU - Klocperk, Adam

AU - Marzollo, Antonio

AU - Marcus, Nufar

AU - Nademi, Zohreh

AU - Schmid, Jana Pachlopnik

AU - Pichler, Herbert

AU - Sellmer, Anna

AU - Soler-Palacin, Pere

AU - Soomann, Maarja

AU - Torpiano, Paul

AU - van Montfrans, Joris

AU - Nierkens, Stefan

AU - Adams, Stuart

AU - Buckland, Matthew

AU - Gilmour, Kimberly

AU - Worth, Austen

AU - Thrasher, Adrian J

AU - Davies, E Graham

AU - André, Isabelle

AU - Kreins, Alexandra Y

PY - 2025/2/16

Y1 - 2025/2/16

N2 - 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.

AB - 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.

U2 - 10.1016/j.clim.2025.110453

DO - 10.1016/j.clim.2025.110453

M3 - Article

C2 - 39965724

SN - 1521-6616

VL - 274

JO - Clinical Immunology

JF - Clinical Immunology

M1 - 110453

ER -

Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia

Abstract

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