Abstract 17293: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Donor Specific Antibodies
Bibliographic record
Abstract
Introduction: Human Leukocyte Antigen (HLA)-G is a natural immune regulator that inhibits T cells, NK cells and B cell activity. In the context of transplantation, less rejection and better graft outcomes are associated with higher serum levels of HLA-G. The association between HLA-G polymorphisms in the recipient and donor and post-transplant donor specific antibodies (DSA) has never been explored. DSA can lead to antibody-mediated rejection and are associated with worse outcomes. Objective: to determine the association between HLA-G single nucleotide polymorphisms (SNPs) in the recipient and donor and DSA. Methods: 251 adult heart recipients and 196 matching donors were evaluated for various HLA-G SNPs. Serum from patient and donor were tested for positive presence of HLA Class I antibodies. DNA was genotyped for 14bp INDEL, G*01:01, G*01:04 and G*0:05N. The analysis was performed first in univariable regression models and then in multivariable regression model using a backward selection approach of potential risk factors with a univariable associations with p-value <0.10. The model automatically included time since transplantation as an obligatory covariate. Results: General characteristics: recipient age 48.2±12.1 years, 69% males and donor age 35.5±14.3 years. Of those, 19 (8%) had at least one positive DSA diagnosis. In a multivariable analysis adjusted for time since transplant, documented non-compliance and blood group A, the presence of donor G*01:04 allele was identified with a protective role for the development of DSA (0.079, CI 0.02-0.39, p= 0.002). Patient allele G*01:05N was associated with increased risk for DSA (12.95, CI 2.36-71.00, p= 0.003). Lastly, donor SNP 14bp (DEL vs INDEL/INS) was independently associated as a risk factor for DSA (5.75, CI 1.70-19.36, p= 0.005). Conclusions: Three SNPs from the donor and recipient were identified to influence the development of donor specific antibodies. This is the first study to investigate the association of HLA-G to the development of donor specific antibodies and to demonstrate both detrimental and beneficial roles for HLA-G polymorphisms.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.015 | 0.001 |
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.
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".