Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort
Bibliographic record
Abstract
OBJECTIVE: There are limited data on genetic predictors of radiographic progression. The aim of this study was to examine polymorphisms in genes involved in antigen presentation and their effect on radiographic severity and progression. METHODS: Caucasian patients with ankylosing spondylitis (AS) (diagnosed according to the modified New York criteria) from 2 Canadian centers were enrolled. Patients in the progression part of the study had at least 2 sets of radiographs obtained at a minimum gap of 1.5 years, with a modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Peripheral blood DNA was used for genotyping a panel of 13 coding-region single-nucleotide polymorphisms (SNPs) in ERAP1, LMP2, LMP7, TAP1, and TAP2. Linear regression analysis was performed to identify the predictors of the baseline mSASSS and logistic regression for predictors of progression. Progression was defined as an increase of 1 mSASSS unit per year. RESULTS: A total of 241 AS patients (81% males; 82% HLA-B27-positive) were enrolled from the 2 centers for analysis of the predictors of baseline radiographic severity. In univariate analyses, the baseline mSASSS was associated with sex, disease duration, and SNPs rs30187 (ERAP1) and rs17587 (LMP2). In multivariate analyses, duration of disease (B = 0.74; P = 1 × 10(-11) ), sex (B = 12.1; P = 5 × 10(-5) ), and the LMP2 SNP rs17587 (B = 6.2; P = 0.01) were significantly associated with the baseline mSASSS. In multivariate analyses of progression, only the baseline mSASSS was a significant predictor (B = 0.03; P = 0.003). CONCLUSION: This is the first study to demonstrate that LMP2 variants can affect radiographic severity in AS. The baseline mSASSS remains the strongest predictor of radiographic progression but explains only a fraction of the variability seen.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".