Intest Res.  2024 Oct;22(4):464-472. 10.5217/ir.2023.00139.

Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn’s disease small bowel lesion in capsule endoscopy

Affiliations
  • 1Department of Gastroenterology and Hepatology, Kyorin University Suginami Hospital, Kyorin University School of Medicine, Tokyo, Japan
  • 2Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan

Abstract

Background/Aims
Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn’s disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE.
Methods
Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated.
Results
Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 μg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 μg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman’s rank correlation coefficient ρ = 0.681, P< 0.001).
Conclusions
An LRG cutoff value of 14 μg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 μg/mL may be useful in predicting the absence of SB inflammatory findings.

Keyword

Capsule endoscopy; Leucine-rich alpha-2 glycoprotein; Crohn’s disease activity in capsule endoscopy; Crohn disease; Small bowel

Figure

  • Fig. 1. Study profile. Intestinal patency was evaluated by patency capsule in all cases. CD, Crohn’s disease; SB, small bowel; SBCE, SB capsule endoscopy; LRG, leucine-rich alpha-2 glycoprotein.

  • Fig. 2. Receiver operating characteristic curve of CDAI, CRP, and LRG for small bowel ulcer (≥0.5 cm). The highest AUC value was 0.92 at an LRG value of 14 μg/mL. CDAI, Crohn’s Disease Activity Index; CRP, C-reactive protein; LRG, leucine-rich alpha-2 glycoprotein; AUC, area under the curve.

  • Fig. 3. Receiver operating characteristic curve of leucine-rich alpha-2 glycoprotein (LRG) levels for the absence of small bowel inflammatory findings in patients with Crohn’s disease. The maximum area under the curve (AUC) value was 0.87 at an LRG value of 12 μg/mL.

  • Fig. 4. Correlation between CDACE and LRG (Spearman's rank correlation coefficient). CDACE, Crohn’s Disease Activity in Capsule Endoscopy; LRG, leucine-rich alpha-2 glycoprotein.

  • Fig. 5. Prediction of the presence of SB lesions based on LRG values and proposed interpretation. aMinor inflammatory lesions: edema, erythema, erosions (<0.5 cm mucosal lesions). SB, small bowel; SBCE, SB capsule endoscopy; LRG, leucine-rich alpha-2 glycoprotein; PPV, positive predictive value; NPV, negative predictive value; +LR, positive likelihood ratio; –LR, negative likelihood ratio.


Reference

1. Matsuoka K, Fujii T, Okamoto R, et al. Characteristics of adult patients newly diagnosed with Crohn’s disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn’s disease in Japan (iCREST-CD). J Gastroenterol. 2022; 57:867–878.
2. Takenaka K, Ohtsuka K, Kitazume Y, et al. Utility of magnetic resonance enterography for small bowel endoscopic healing in patients with Crohn’s disease. Am J Gastroenterol. 2018; 113:283–294.
3. Yang DH, Yang SK, Park SH, et al. Usefulness of C-reactive protein as a disease activity marker in Crohn’s disease according to the location of disease. Gut Liver. 2015; 9:80–86.
4. Lewis JD, Rutgeerts P, Feagan BG, et al. Correlation of stool frequency and abdominal pain measures with simple endoscopic score for Crohn’s disease. Inflamm Bowel Dis. 2020; 26:304–313.
5. Kopylov U, Yablecovitch D, Lahat A, et al. Detection of small bowel mucosal healing and deep remission in patients with known small bowel Crohn’s disease using biomarkers, capsule endoscopy, and imaging. Am J Gastroenterol. 2015; 110:1316–1323.
6. Shinzaki S, Matsuoka K, Iijima H, et al. Leucine-rich alpha-2 glycoprotein is a serum biomarker of mucosal healing in ulcerative colitis. J Crohns Colitis. 2017; 11:84–91.
7. Serada S, Fujimoto M, Ogata A, et al. iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2010; 69:770–774.
8. Omori T, Sasaki Y, Koroku M, et al. Serum leucine-rich alpha-2 glycoprotein in quiescent Crohn’s disease as a potential surrogate marker for small-bowel ulceration detected by capsule endoscopy. J Clin Med. 2022; 11:2494.
9. Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther. 2008; 27:146–154.
10. Gal E, Geller A, Fraser G, Levi Z, Niv Y. Assessment and validation of the new Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI). Dig Dis Sci. 2008; 53:1933–1937.
11. Omori T, Matsumoto T, Hara T, et al. A novel capsule endoscopic score for Crohn’s disease. Crohns Colitis 360. 2020; 2–otaa040.
12. Okita M, Nakashima K, Yamamura T, Matsui S. Systematic review and meta-analysis of the use of serum leucine-rich alpha-2 glycoprotein to assess Crohn’s disease activity. Inflamm Bowel Dis. 2024; 30:780–787.
13. Shimoyama T, Yamamoto T, Yoshiyama S, Nishikawa R, Umegae S. Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for evaluating clinical and endoscopic disease activity in inflammatory bowel disease. Inflamm Bowel Dis. 2023; 29:1399–1408.
14. Abe I, Shiga H, Chiba H, et al. Serum leucine-rich alpha-2 glycoprotein as a predictive factor of endoscopic remission in Crohn’s disease. J Gastroenterol Hepatol. 2022; 37:1741–1748.
15. Kawamoto A, Takenaka K, Hibiya S, Ohtsuka K, Okamoto R, Watanabe M. Serum leucine-rich α2 glycoprotein: a novel biomarker for small bowel mucosal activity in Crohn’s disease. Clin Gastroenterol Hepatol. 2022; 20:e1196–e1200.
16. Yasutomi E, Inokuchi T, Hiraoka S, et al. Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. Sci Rep. 2021; 11:11086.
17. Kawamura T, Yamamura T, Nakamura M, et al. Accuracy of serum leucine-rich alpha-2 glycoprotein in evaluating endoscopic disease activity in Crohn’s disease. Inflamm Bowel Dis. 2023; 29:245–253.
18. Asonuma K, Kobayashi T, Kikkawa N, et al. Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn’s disease. Inflamm Intest Dis. 2023; 8:13–22.
19. Takenaka K, Kitazume Y, Kawamoto A, et al. Serum leucine-rich α2 glycoprotein: a novel biomarker for transmural inflammation in Crohn’s disease. Am J Gastroenterol. 2023; 118:1028–1035.
20. Ito T, Dai K, Horiuchi M, Horii T, Furukawa S, Maemoto A. Monitoring of leucine-rich alpha-2-glycoprotein and assessment by small bowel capsule endoscopy are prognostic for Crohn’s disease patients. JGH Open. 2023; 7:645–651.
21. Kawamoto A, Takenaka K, Hibiya S, et al. Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn’s disease activity confirmed by balloon-assisted enteroscopy. Intest Res. 2024; 22:65–74.
22. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021; 160:1570–1583.
23. Leenhardt R, Buisson A, Bourreille A, et al. Nomenclature and semantic descriptions of ulcerative and inflammatory lesions seen in Crohn’s disease in small bowel capsule endoscopy: an international Delphi consensus statement. United European Gastroenterol J. 2020; 8:99–107.
24. Leenhardt R, Koulaouzidis A, McNamara D, et al. A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire. Clin Res Hepatol Gastroenterol. 2021; 45:101637.
Full Text Links
  • IR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr