# Leucine-Rich α2 Glycoprotein as a Predictor of Small Bowel Disease Activity in Crohn’s Disease: A Retrospective Study

**Authors:** Tomoyuki Hayashi, Kazuya Kitamura, Masaaki Usami, Noriaki Orita, Hidetoshi Nakagawa, Masaki Miyazawa, Hajime Takatori, Masaki Nishitani, Akihiro Dejima, Tetsuro Shimakami, Kosuke Satomura, Makiko Kimura, Hirofumi Okafuji, Hiroto Saito, Daisuke Yamamoto, Noriyuki Inaki, Tadashi Toyama, Taro Yamashita

PMC · DOI: 10.31662/jmaj.2025-0355 · JMA Journal · 2025-12-05

## TL;DR

This study shows that leucine-rich α2 glycoprotein (LRG) is a non-invasive biomarker that can accurately predict small bowel disease activity in Crohn’s disease patients.

## Contribution

LRG is shown to outperform conventional biomarkers in diagnosing and predicting disease activity in Crohn’s disease.

## Key findings

- LRG demonstrated the highest diagnostic accuracy with an AUC of 0.906.
- Elevated LRG levels were independently associated with endoscopic activity (odds ratio: 36.4).
- High LRG levels predicted poorer hospitalization-free and surgery-free survival.

## Abstract

Balloon-assisted enteroscopy is the gold standard for evaluating small bowel lesions in Crohn’s disease (CD); however, its invasiveness and cost limit routine use. Leucine-rich α-2 glycoprotein (LRG) has emerged as a potential noninvasive biomarker. This study aimed to assess the diagnostic utility of LRG compared with conventional biomarkers.

This retrospective study included 216 patients with CD who underwent balloon-assisted enteroscopy between April 2021 and March 2024. Serum biomarkers, including LRG, C-reactive protein, leukocyte count, neutrophil count, hemoglobin, platelet count, erythrocyte sedimentation rate, and albumin, were analyzed. Endoscopic activity was defined as mucosal ulcers measuring ≥0.5 cm. Diagnostic performance was evaluated using receiver operating characteristic curve analysis, and predictors of endoscopic activity were identified using multivariate logistic regression. Prognostic value was assessed using hospitalization-free and surgery-free survival.

LRG demonstrated the highest diagnostic accuracy (area under the ROC curve (AUC), 0.906), outperforming C-reactive protein ( area under the receiver operating characteristic curve: 0.776). An LRG cutoff of 16.3 μg/mL yielded 72.1% sensitivity and 93.7% specificity. Elevated LRG was independently associated with endoscopic activity (odds ratio: 36.4, p < 0.001) and correlated with higher modified Simple Endoscopic Score for Crohn’s disease (mSES-CD). High LRG levels were also predictive of poorer hospitalization-free and surgery-free survival.

LRG is a reliable and non-invasive biomarker for assessing small bowel disease activity in CD, showing superior diagnostic and prognostic performance compared with conventional biomarkers. It may be a valuable adjunct to endoscopic and imaging evaluations in clinical practice.

## Linked entities

- **Proteins:** LRG1 (leucine rich alpha-2-glycoprotein 1)
- **Diseases:** Crohn’s disease (MONDO:0005011)

## Full-text entities

- **Genes:** LRG1 (leucine rich alpha-2-glycoprotein 1) [NCBI Gene 116844] {aka HMFT1766, LRG}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** mucosal ulcers (MESH:D014456), Small Bowel Disease (MESH:D015212), CD (MESH:D003424)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12889229/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12889229/full.md

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Source: https://tomesphere.com/paper/PMC12889229