Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopenia
Bibliographic record
Abstract
Abstract Newborn screening for severe combined immunodeficiency promotes early diagnosis and timely treatment, improving clinical outcomes. Selective T-lymphocytopaenia is found both in haematopoietic cell-intrinsic and thymic stromal cell-intrinsic defects, including congenital athymia which is associated with a T-B + NK + immunophenotype. Without a molecular diagnosis, it is challenging to determine whether haematopoietic cell transplantation (HCT) or thymus transplantation ought to be performed. Ex vivo T-lymphocyte differentiation assays have been proposed to assist clinical decision-making for genetically undefined T-lymphocytopaenic patients by assessing the intrinsic potential of their haematopoietic progenitors to differentiate into mature T-lymphocytes. We investigated 18 T-lymphocytopaenic patients, including 12 patients awaiting first-line treatment and 6 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst early developmental blocks in ex vivo T-lymphopoiesis indicated haematopoietic cell-intrinsic defects, successful differentiation of mature T-lymphocytes required careful interpretation, in conjugation with clinical status and presentation, immunophenotyping, and available genetic investigations. 5 patients were referred for HCT and 12 for thymus transplantation. 12/18 patients proceeded to treatment with successful immune reconstitution in 4/5 patients after HCT and 4/7 after thymus transplantation, the latter including two patients previously treated with HCT. Two treated patients died, either after HCT or after thymus transplantation, due to pre-existing complications, and two patients have yet to show immune reconstitution seven months and one year after thymus transplantation respectively. Overall, we conclude that including ex vivo T-lymphocyte differentiation assays in the diagnostic pathway for genetically undefined T-lymphocytopaenia improves patient outcomes by facilitating corrective treatment choice between HCT and thymus transplantation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".