HLA HOMOZYGOSITY IS ASSOCIATED WITH INCREASED RISK AND SEVERITY OF SYSTEMIC LUPUS ERYTHEMATOSUS
Bibliographic record
Abstract
PV104 / #455 Poster Topic: AS12 - Genetics, Epigenetics, Transcriptomics Background/Purpose The risk of systemic lupus erythematosus (SLE) involves both environmental and genetic factors, yet the etiology remains largely unknown. Previous genome-wide association studies have revealed strong associations between SLE and the major histocompatibility complex (MHC) region. Meanwhile, loss of heterozygosity at the human leukocyte antigen (HLA) loci has been extensively studied in the field of oncology, correlated with dysregulated immune response and an elevated susceptibility to various malignancies. The aim of this study was to identify the association between homozygosity of HLA genes and the onset and clinical manifestations of SLE. Methods MHC-targeted sequencing or whole exome sequencing (WES) was performed for 1409 SLE patients and 6084 healthy controls. HLA alleles and amino acid sequences were identified, and rate of homozygosity was compared between SLE patients and healthy controls. The results were validated in an independent cohort consisting of 1303 SLE patients and 4832 healthy controls. Data on disease activity, organ damage and autoantibody profile were collected during a follow-up of over 5 years for the discovery cohort, and the association between HLA homozygosity and clinical manifestations was investigated. Results Homozygosity of HLA-A, B, C, DQA1, and DRB1 was associated with increased risk of SLE in both the discovery and validation cohort. Among SLE patients, homozygosity of HLA-A, DQA1, and DRB1 was associated with an earlier age of onset. Homozygosity of HLA-DQA1 and homozygosity across all HLA alleles were associated with greater maximum SLE Disease Activity Score (SLEDAI) during the course of disease. With respect to organ involvement, homozygosity of certain HLA genes was identified as risk factor for myopathy, serositis, ophthalmic diseases, while homozygosity of certain other HLA genes conferred protection against alopecia, leukopenia, thrombosis, etc. Homozygosity of certain amino acid loci within the peptide binding groove was also associated with increased risk of SLE. Conclusions Homozygosity of certain class I and class II HLA genes is associated with increased risk of SLE, earlier age of onset, and exacerbated clinical manifestations among SLE patients.
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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 | 0.000 | 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) | 0.006 | 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".