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Missing KIR ligand in the host-versus-graft (HvG) direction is associated with second cell infusion in children with NK+ severe combined immunodeficiency (SCID) receiving hematopoietic stem cell transplantation.

2017· article· en· W4313384741 on OpenAlexaff
Justin T. Wahlstrom, Henry V. Bender, Ziyan Yin, Brent R. Logan, Raja Rajalingam, Christopher C. Dvorak, Élie Haddad, Morton J. Cowan

Bibliographic record

VenueThe Journal of Immunology · 2017
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsHuman leukocyte antigenHematopoietic stem cell transplantationTransplantationTypingImmunologyT cellLigand (biochemistry)MedicineImmune systemBiologyInternal medicineReceptorAntigenGenetics

Abstract

fetched live from OpenAlex

Abstract Functional NK cells are thought to mediate graft rejection in allogeneic hematopoietic stem cell transplantation (HSCT) for SCID. We hypothesized that missing KIR ligand (MKL) in the HvG direction mediates NK alloreactivity and is associated with increased rates of 2nd cell infusion requirement in NK+ SCID patients treated with HSCT. Data collected by the Pediatric Immune Deficiency Treatment Consortium (PIDTC) from 1982 to 2012 were reviewed. A total of 174 NK+ SCID transplant recipients were identified. Of these, HLA-B typing was available for 172 recipient/donor pairs, and HLA-C typing was available for 131 pairs. MKL was identified if Bw4, C1, or C2 inhibitory ligands were present in the recipient but not the donor. MKL was identified for Bw4 in 18 of 172 donors; for C1 in 11 of 131 donors; and for C2 in 9 of 131 donors. Combined Bw4, C1, and C2 MKL analysis was feasible for 129 transplants; 38 of these donors were missing one or two ligands in the HvG direction. Missing Bw4 ligand alone was not associated with decreased EFS or increased need for 2nd cell infusion. The incidence of 2nd infusion at 2 years was significantly lower for pairs without missing HLA-B or HLA-C ligands (19.3%, 95% CI 11.8% – 28.2%) compared to those with MKL (28.9%, 95% CI 15.5% – 43.9%; Gray’s p=0.04). EFS was 63.2% in patients with MKL (95% CI 45.9% – 76.3%) and 75.2% in those without MKL (95% CI 64.7% – 82.9%; Gray’s p=0.05). Missing KIR ligand in the HvG direction is associated with 2nd cell infusion in HSCT for NK+ SCID and may represent a mechanism for NK alloreactivity in this setting. Multivariate analysis and biologic studies of NK reactivity in SCID patients are needed to better understand the role of recipient NK cells in HSCT.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.008
GPT teacher head0.211
Teacher spread0.202 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations0
Published2017
Admission routes1
Has abstractyes

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