Role of leucine-rich α-2-glycoprotein in Taiwanese patients with inflammatory bowel disease as a predictive biomarker for endoscopic activity

doi:10.3748/wjg.v32.i3.114677

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 21, 2026; 32(3): 114677
Published online Jan 21, 2026. doi: 10.3748/wjg.v32.i3.114677

Role of leucine-rich α-2-glycoprotein in Taiwanese patients with inflammatory bowel disease as a predictive biomarker for endoscopic activity

Yun-Chu Chen, Meng-Tzu Weng, Feng-Pai Tsai, Zhi-Che Chen, Hsin-Yun Wu, Chien-Chih Tung, Chun-Ying Wang, Shu-Chen Wei

Yun-Chu Chen, Meng-Tzu Weng, Feng-Pai Tsai, Zhi-Che Chen, Hsin-Yun Wu, Shu-Chen Wei, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan

Meng-Tzu Weng, Chun-Ying Wang, Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan

Feng-Pai Tsai, Department of Medicine, National Taiwan University Cancer Center, Taipei 106, Taiwan

Zhi-Che Chen, Hsin-Yun Wu, Department of Internal Medicine, National Taiwan University Hospital Jin-Shan Branch, New Taipei City 208, Taiwan

Chien-Chih Tung, Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 100, Taiwan

Author contributions: Chen YC, Tsai FP, and Wei SC contributed to the conceptualization; Chen YC, Chen ZC, and Wu HY contributed to data curation; Chen YC and Wang CY contributed to formal analysis; Tsai FP, Tung CC, and Wei SC contributed to investigation; Weng MT, Tung CC, and Wei SC contributed to resources; Chen YC, Weng MT, Wu HY, and Wei SC contributed to supervision; Chen YC wrote the original draft; Weng MT, Chen ZC, Wu HY, and Wei SC contributed to writing - review & editing.

Supported by the National Science and Technology Council of Taiwan, No. MOST 111-2314-B-002-188-MY3; and the Liver Disease Prevention and Treatment Research Foundation.

Institutional review board statement: This study was approved by the Institutional Review Board of National Taiwan University Hospital (approval No. 202112116RINC).

Clinical trial registration statement: This study is not a clinical trial.

Informed consent statement: This prospective study was conducted in accordance with the ethical principles for medical research involving human patients outlined in the Declaration of Helsinki, which was updated in 2013. Written informed consent was obtained from all participants before enrollment.

Conflict-of-interest statement: Wei SC received research grants from the National Science and Technology Council of Taiwan (No. MOST 111-2314-B-002-188-MY3), National Taiwan University Hospital (No. MS 507) and the Liver Disease Prevention and Treatment Research Foundation to support this study.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: The technical appendix, statistical code, and dataset that support the findings of this study are available from the corresponding author upon reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Shu-Chen Wei, MD, PhD, Professor, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chungshan South Road, Taipei 100, Taiwan. shuchenwei@ntu.edu.tw

Received: September 26, 2025
Revised: October 24, 2025
Accepted: December 2, 2025
Published online: January 21, 2026
Processing time: 113 Days and 0.4 Hours

Abstract

BACKGROUND

Endoscopy is the gold standard for examining inflammatory bowel disease (IBD), and fecal calprotectin (FC) is a widely used surrogate marker for IBD. However, both methods are considered unpleasant by patients because of their invasiveness and inconvenience. Leucine-rich α-2-glycoprotein (LRG) is a novel serum biomarker that has been previously studied only in Japanese populations.

AIM

To evaluate the predictive utility of LRG in a Taiwanese cohort.

METHODS

Patients with IBD were prospectively enrolled between 2022 and 2024. Serum and stool samples were collected within 1 month of endoscopy, and patient albumin, hemoglobin (Hb), and C-reactive protein (CRP) levels were measured. Active endoscopic disease was defined as a Mayo endoscopic subscore ≥ 2 for ulcerative colitis (UC) or a Simple Endoscopic Score for Crohn’s Disease ≥ 6 for Crohn’s disease (CD). Correlations and diagnostic performance of biomarkers were analyzed.

RESULTS

A total of 203 patients (100 with UC and 103 with CD) were enrolled. LRG was positively correlated with FC and CRP but negatively correlated with Hb and albumin (P < 0.05). In UC, the area under the curves (AUCs) for CRP, LRG, and FC in predicting endoscopic activity were 0.54, 0.56, and 0.77, respectively (P < 0.001). In CD, the corresponding AUCs were 0.69, 0.60, and 0.72 (P > 0.05). The addition of LRG modestly improved predictive ability for endoscopic activity in patients with UC. In patients with UC with low CRP levels, combining CRP, Hb, and LRG significantly improved diagnostic accuracy (AUC increased from 0.60 to 0.76, P < 0.05), achieving a performance comparable to, though slightly lower than, that of FC (AUC: 0.78).

CONCLUSION

LRG may serve as a supportive biomarker, particularly in combination with other markers, for assessing disease activity in Taiwanese patients with IBD. In patients with UC with normal CRP levels, adding LRG and Hb could enhance the predictive accuracy for endoscopic activity to nearly that of FC.

Keywords: Leucine-rich α-2-glycoprotein; Ulcerative colitis; Crohn’s disease; Inflammatory bowel disease; Biomarkers

Core Tip: Endoscopy and fecal calprotectin (FC) are standard tools for assessing disease activity in inflammatory bowel disease (IBD) but both have limitations. We evaluated serum leucine-rich α-2-glycoprotein (LRG) as a noninvasive biomarker in a Taiwanese IBD cohort. LRG correlated with FC, C-reactive protein (CRP), hemoglobin, and albumin. In ulcerative colitis, LRG predicted endoscopic activity, particularly in patients with normal CRP levels. Combining CRP, hemoglobin, and LRG significantly improved the endoscopic activity prediction to nearly that of FC. Our findings support the clinical utility of LRG as a complementary biomarker for disease monitoring in IBD, particularly in ulcerative colitis with low CRP.