Intest Res.  2024 Jan;22(1):65-74. 10.5217/ir.2023.00092.

Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn’s disease activity confirmed by balloon-assisted enteroscopy

• Kawamoto A
• Takenaka K
• Hibiya S
• Kitazume Y
• Shimizu H
• Fujii T
• Saito E
• Ohtsuka K
• Okamoto R

• KMID: 2551279
• DOI: http://doi.org/10.5217/ir.2023.00092

Abstract

Background/Aims
Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.
Methods
One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.
Results
Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.
Conclusions
The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.

Keyword

Crohn disease; Leucine-rich alpha2-glycoprotein, human; Leukocyte L1 antigen complex; Biomarkers; Inflammatory bowel diseases

Figure

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  Fig. 1. Blood and fecal biomarkers detect Crohn’s disease patients with intestinal ulcers. Box and whisker plots showing levels of serum CRP (A), serum LRG (B), fecal hemoglobin (C), fecal calprotectin (D), hemoglobin (E), and platelet count (F) determined in patients in whom no ulcers were observed with enteroscopy (n=49) and in patients with confirmed ulcers (n=55). CRP, C-reactive protein; LRG, leucine-rich alpha-2 glycoprotein.

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  Fig. 2. Fecal calprotectin and LRG show a stronger correlation with endoscopic severity compared to the other biomarkers. Scatterplots showing the correlation of serum CRP (A), serum LRG (B), fecal hemoglobin (C), fecal calprotectin (D), hemoglobin (E), and platelet count (F) with modified SES-CD (r=Spearman rank correlation coefficient). LRG, leucine-rich alpha-2 glycoprotein; CRP, C-reactive protein; SES-CD, Simple Endoscopic Score for Crohn’s Disease.

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  Fig. 3. Kaplan-Meier curves demonstrating poorer outcome-free survival for patients with high leucine-rich alpha-2 glycoprotein (LRG) and fecal calprotectin levels compared with patients who have low LRG and/or fecal calprotectin levels (A-C), and those with high LRG and fecal hemoglobin levels compared with patients who have low LRG and/or fecal hemoglobin levels (D-F) (P<0.05 for all).

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