RARE VARIANTS OF PAH RISK GENES ASSOCIATE WITH A DISTINCT VASCULOPATHY PHENOTYPE AND WORSE OUTCOMES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION
Bibliographic record
Abstract
PV109 / #563 Poster Topic: AS12 - Genetics, Epigenetics, Transcriptomics Background/Purpose Systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) displays significant clinical heterogeneity; Presently, more than 20 risk genes have been identified to be closely linked to the pathogenesis and prognosis of idiopathic and familial PAH. However, the role of rare variants of PAH risk genes in SLE-associated PAH remains largely unknown. Methods Based on the Chinese SLE Treatment and Research Group (CSTAR)-PAH cohort, 241 patients with SLE-associated PAH were recruited and screened for rare deleterious variants in 28 known PAH risk genes by whole exome sequencing. Clinical features, hemodynamic characteristics and outcomes were compared between variant carriers and noncarriers. Another 87 patients with SLE-associated PAH were included as genetic replication cohort. Results 51 patients of SLE-associated PAH (21.5%) carried rare variants of PAH risk genes, which is significantly higher than control group (13.9%, P=0.009). This finding was replicated in the independent validation cohort. Among patients with SLE-associated PAH, carriers had a shorter PAH duration from SLE onset, a higher proportion of PAH as the onset symptom of SLE and lower SLE disease activity. Carrying rare variants of PAH risk genes was identified as an independent prognostic factor of mortality (hazard ratio [HR]=3.13, 95% CI, 1.10-8.97; P=0.005) and of poor treatment response to immunosuppressants, defined as the proportion of patients reaching a low risk profile of PAH according to the ESC/ERS guidelines (HR=0.56, 95% CI 0.34-0.94, P=0.027). Conclusions We showed for the first time that rare variants of PAH risk genes associated with a distinct vasculopathy phenotype and worse outcomes in patients with SLE-associated PAH, highlighting the significant clinical value in molecular classification and supporting future research on personalized strategies based on genetic and clinical characteristics in SLE-associated PAH.
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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 | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".