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Record W4407607321 · doi:10.1016/j.clim.2025.110453

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

2025· article· en· W4407607321 on OpenAlexaff
Zainab Golwala, Helena Spiridou Goncalves, Ranjita Devi Moirangthem, Grace Evans, Sabrina Lizot, Coco de Koning, Alexandrine Garrigue, Marta Martin Corredera, Juan Moisés Ocampo‐Godínez, Evey Howley, Susanne Kricke, Irene Obiri-Yeboa, Rajeev Rai, Neil J. Sebire, Fanette Bernard, Kaan Boztuǧ, Theresa Cole, Andrew R. Gennery, Scott Hackett, Sophie Hambleton, Mette Holm, Maaike Kusters, Adam Klocperk, Antonio Marzollo, Nufar Marcus, Zohreh Nademi, Jana Pachlopnik Schmid, Herbert Pichler, Anna Sellmer, Pere Soler‐Palacín, 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‐Schmutz, Alexandra Y. Kreins

Bibliographic record

VenueClinical Immunology · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsInstitute of Infection and Immunity
FundersMedical Research CouncilGreat Ormond Street Hospital CharityWellcome Trust
KeywordsEx vivoLymphopoiesisGenetically engineeredGenetically modified organismImmunologyBiologyIn vivoCell biologyHaematopoiesisStem cellGeneticsGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.833
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.037
GPT teacher head0.351
Teacher spread0.313 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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