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Record W4401968543 · doi:10.3389/fgene.2024.1447141

HLA-DR/DQ eplet mismatch predicts de novo donor-specific antibody development in multi-ethnic Southeast Asian kidney transplant recipients on different immunosuppression regimens

2024· article· en· W4401968543 on OpenAlexaff
Emmett Tsz Yeung Wong, Denise Pochinco, Anantharaman Vathsala, Wee Kun Koh, Amy Lim, Hersharan Kaur Sran, Matthew R. D’Costa, Zi Yun Chang, Peter Nickerson, Chris Wiebe

Bibliographic record

VenueFrontiers in Genetics · 2024
Typearticle
Languageen
FieldMedicine
TopicRenal Transplantation Outcomes and Treatments
Canadian institutionsManitoba HealthUniversity of Manitoba
Fundersnot available
KeywordsMedicineCohortHuman leukocyte antigenImmunosuppressionAlloimmunityInternal medicineOncologyImmunologyTransplantationAntigen

Abstract

fetched live from OpenAlex

Eplet mismatch has been recognized as a more precise strategy for determining HLA compatibility by analyzing donor-recipient HLA differences at the molecular level. However, predicting post-transplant alloimmunity using single-molecule eplet mismatch categories has not been validated in Asian cohorts. We examined a cohort of Southeast Asian kidney transplant recipients (n = 234) to evaluate HLA-DR/DQ eplet mismatch as a predictor of de novo donor-specific antibody (dnDSA) development. HLA-DR/DQ single-molecule eplet mismatch was quantified using HLA Matchmaker, and we utilized previously published HLA-DR/DQ eplet mismatch thresholds to categorize recipients into alloimmune risk groups and evaluate their association with dnDSA development. Recognizing that the predominance of cyclosporine use (71%) may alter published eplet mismatch thresholds derived from a largely tacrolimus-based (87%) cohort, we evaluated cohort-specific thresholds for HLA-DR/DQ single-molecule eplet mismatch categories. Recipient ethnicities included Chinese (65%), Malays (17%), Indians (14%), and others (4%). HLA-DR/DQ dnDSA developed in 29/234 (12%) recipients after a median follow-up of 5.4 years, including against isolated HLA-DR (n = 7), isolated HLA-DQ (n = 11), or both (n = 11). HLA-DR/DQ single-molecule eplet mismatch risk categories correlated with dnDSA-free survival (p = 0.001) with low-risk recipients having a dnDSA prevalence of 1% over 5 years. The cohort-specific alloimmune risk categories improved correlation with HLA-DR/DQ dnDSA-free survival and remained significant after adjusting for calcineurin inhibitor and anti-metabolite immunosuppression (p < 0.001). We validated the performance of single-molecule eplet mismatch categories as a prognostic biomarker for HLA-DR/DQ dnDSA development in a cohort of predominantly Asian kidney transplant recipients after adjusting for different immunosuppression regimens.

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)0.001
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 score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.032
GPT teacher head0.305
Teacher spread0.273 · 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

Citations14
Published2024
Admission routes1
Has abstractyes

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