Enrichment of Variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU Patients: An Exploratory Study
Bibliographic record
Abstract
Background: Infection by the pandemic influenza A (H1N1/09) virus resulted in significant pathology among specific ethnic groups worldwide.Natural Killer (NK) cells are important in early innate immune responses to viral infections.Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR) and HLA class I ligand interactions.To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU) patients were determined.Methodology and Findings: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1negative subjects (St.Theresa Point, Manitoba) were characterized.We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1 + Bw6 + Bw4 2 ), and a lack of 2DL1 HLA-C2 ligands, among ICU patients.They were also significantly enriched for 2DL2/L3 ligand-positive pairs (P,0.001,Pc,0.001;Odds Ratio:6.3158,CI95%:2.481-16.078).Relative to St. Theresa aboriginals (STh) and Venezuelan Amerindians (VA), allotypes enriched among aboriginal ICU patients (Ab) were: 2DL3 (Ab.VA, P = 0.024, Pc = 0.047; Odds Ratio:2.563,CI95%:1.109-5.923),3DL1*00101 (Ab.VA, P,0.001, Pc,0.001), 3DL1*01502 (Ab.STh, P = 0.034, Pc = 0.268), and 3DL1*029 (Ab.STh, P = 0.039, Pc = 0.301).Aboriginal patients ligandpositive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R d ) (R d = 28%), compared to patients that were 3DL1/ S1 ligand-negative (R d = 52%) or carried 3DL1*029 (R d = 52%).Relative to Caucasoids (CA), two allotypes were enriched among non-aboriginal ICU patients (NAb): 3DL1*00401 (NAb.CA, P,0.001, Pc,0.001) and 3DL1*01502 (CA,NAb, P = 0.012, Pc = 0.156).Non-aboriginal patients with ligands for all three KIRs (3DL1/S1, 2DL2/L3, and 2DL1) had the lowest probabilities of death (R d = 36%), compared to subjects with 3DL1*01502 (R d = 48%) and/or 3DL1*00401 (R d = 58%).Conclusions: Specific KIR3DL1/S1 allotypes, 3DL1/S1 and 2DL1 ligand-negative pairs, and 2DL2/L3 ligand-positive pairs were enriched among ICU patients.This suggests a possible association with NK cell dysfunction in patients with overactive immune responses to H1N1/09, leading to severe disease.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".