Leucine-Rich Alpha-2 Glycoprotein 1 as a Biomarker for Evaluation of Inflammatory Bowel Disease Activity in Children

Abstract

Background: Leucine rich α-2 glycoprotein (LRG) is a glycoprotein that is an acute-phase protein produced by neutrophils, macrophages, hepatocytes, and intestinal epithelial cells. This study aimed to determine the serum LRG (s-LRG) and urine LRG (u-LRG) expression levels in children with inflammatory bowel disease (IBD) and evaluated their correlation with clinical disease activity, other inflammatory markers, laboratory results, and endoscopic activity scoring. Methods: This prospective observational study was conducted at a tertiary centre and included children aged 2-18 years with IBD. Clinic activity scoring was used to assess clinical disease activity. Haemoglobin levels, platelet counts, albumin, C-reactive protein, and erythrocyte sedimentation rate were analysed in the blood sample. LRG levels were measured in both blood and urine samples. The endoscopic assessment was scored according to the simple endoscopic score and Mayo endoscopic score. Serum and urine LRG levels were measured using commercial enzyme-linked immunosorbent assay kits. Disease activation was defined based on clinical activity scoring, laboratory results, and endoscopic evaluation. The results were compared between the active IBD and remission groups. Results: Forty-two (50%) patients with active IBD and forty-two (50%) patients in remission were included in this study. The serum levels of LRG were elevated in the patients with active IBD compared with the levels in the patients with IBD in remission (p = 0.020). However, there was no difference in the u-LRG level between the two groups (p = 0.407). In patients with IBD, positive correlations were observed between s-LRG, platelet count, C-reactive protein (CRP), and the erythrocyte sedimentation rate. The serum LRG was negatively correlated with albumin and haemoglobin levels. Urine LRG was not correlated with s-LRG in any patients with IBD included or in patients with active IBD. The cutoff value for s- LRG (77.03 μg/mL) had a sensitivity and specificity of 40.4% (95% CI 25.6-56.7%) and 88.1% (95% CI 74.3-96.0%), respectively. It was found that s-LRG was a more significant parameter than CRP in predicting disease activation. Conclusions: This prospective study demonstrated that the s-LRG level is a useful biomarker for predicting disease activation in children with IBD and appears to be a more significant parameter than the CRP level. However, the u-LRG level is not effective in predicting disease activation in children with IBD.

Keywords: biomarker; inflammatory bowel disease; leucine-rich alpha-2 glycoprotein 1.

Figure 1

Correlations of serum leucine-rich alpha-2 glycoprotein 1 with various laboratory tests; s-LRG, serum leucine-rich alpha-2 glycoprotein 1, u-LRG, urine leucine-rich alpha-2 glycoprotein 1; CRP, C-reactive protein, ESR, erythrocyte sedimentation rate. Rs, Spearman’s rank correlation coefficient; the number of subjects was 84 per item.