P0494 Serum regenerating islet-derived 3-alpha (REG3α) is a new prognostic biomarker in Crohn’s Disease
Bibliographic record
Abstract
Abstract Background Regenerating islet-derived 3-alpha (REG3α) is a serum biomarker that, alone or in combination with ST2 (suppressor of tumorigenesis 2), has been used to risk-stratify patients in primary treatment trials for acute graft-versus-host disease (aGVHD) due to its accurate prediction of 6-month non-relapse mortality (1-3). Serum REG3α reflects Paneth cell function and intestinal stem cell niche integrity (4). Given the similarities between intestinal manifestations of aGVHD and Crohn’s disease (CD), we aimed to evaluate the prognostic value of REG3α in CD. Methods We enrolled 231 patients with CD on the Mount Sinai Crohn’s Colitis Registry (MSCCR) at the time of scheduled endoscopic evaluation. We prospectively collected baseline serum samples, and longitudinal clinical data were extracted from structured electronic health records [Table 1]. We used multivariable logistic regression models to investigate associations of IBD progression events, defined as hospitalization, surgery, steroid course, or new biologic, with baseline REG3α levels, controlling for clinical variables [age, biologic use, surgical history, Montreal classification, C-reactive protein (CRP), and endoscopic disease activity (Simple Endoscopic Score, or SES-CD)]. We derived a cutpoint via Youden’s Index to designate high- and low-risk groups by REG3α and used log-rank tests to uncover any difference in times-to-IBD progression event. Results Adjusting for SES-CD, CRP, and age, serum REG3α levels independently associated with adverse IBD outcomes (aOR 1.88, 95% confidence interval [CI] 1.16-3.04, p=0.01)). In subgroups of patients in endoscopic remission (n=124) or with remission+mild endoscopic disease (n=160), REG3α still significantly associated with IBD progression events (aOR 1.89 (95% CI: 1.05-3.39, p=0.034) for SES-CD<3; aOR 1.84 (95% CI: 1.14-3.00, p=0.013) for SES-CD<7). We used Youden’s index to derive a prognostic REG3α cutpoint of 30.29 ng/mL, with sensitivity 0.63 and specificity 0.62, to identify patients at risk of adverse IBD outcomes. High REG3α above the cutpoint conveyed increased hazards of IBD disease progression events (HR 1.91 (95%CI 1.33-2.75, p<0.001 via log-rank test, Figure 1) at median 6.5 (interquartile range (IQR), 3-8) years of follow-up. Conclusion REG3α has potential as a non-invasive, prognostic biomarker in CD, independent of endoscopic inflammation. Elevated REG3α levels were associated with an increased risk of IBD-related disease progression events, including shorter time until IBD surgery, hospitalization, steroid course, or biologic use. References (1)Ferrara JLM, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011;118(25):6702-6708. doi: 10.1182/blood-2011-08-375006 (2)Major-Monfried H, Renteria AS, Pawarode A, et al. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood. 2018;131(25):2846-2855. doi:10.1182/blood-2018-01-822957 (3)Marafini I, Di Sabatino A, Zorzi F, et al. Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies. Aliment Pharmacol Ther. 2014;40(8):974-981. doi:10.111/apt.12920 (4)Zhao D, Kim YK, Jeong S, et al. Survival Signal REG3a prevents crypt apoptotsis to control acute gastrointestinal graft-versus-host disease. J Clin Invest. 2018;128(11):4970-4979. doi:10.1172/JCI99261
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".