LEUCINE-RICH ALPHA 2 GLYCOPROTEIN: A USEFUL BIOMARKER TO DISCRIMINATE SMALL INTESTINAL MUCOSAL HEALING IN C-REACTIVE PROTEIN-NEGATIVE CROHN’S DISEASE

Abstract

Abstract BACKGROUND The treatment goals for inflammatory bowel disease, including Crohn's disease (CD), have shifted from clinical remission to mucosal healing. However, frequent endoscopies burden patients. Leucine-rich alpha 2 glycoprotein (LRG), produced by hepatocytes, neutrophils, and the intestinal epithelium, is more gut-specific than C-reactive protein (CRP). We examined whether LRG, as a biomarker, can detect small intestinal mucosal healing in CD patients, especially in those who are CRP-negative. METHOD 1) This study examined CD patients who visited our department from May 2021 to April 2023, had LRG measured, and underwent image evaluation using capsule endoscopy or balloon-assisted endoscopy. We analyzed their clinical background, looked for a correlation between LRG and CRP, assessed the ROC-AUC of LRG and CRP for mucosal healing, and measured the LRG and CRP cutoff values to determine mucosal healing. 2) Next, in CRP-negative CD patients, we analyzed the ROC-AUC of LRG for mucosal healing and LRG cutoff value to determine mucosal healing. Endoscopic evaluation was done within 3 months before and after LRG measurement. Absent open ulcers indicated mucosal healing. The upper limit of normal CRP value was <3 mg/L. We used the Spearman correlation coefficient to determine the correlation. RESULTS 1) Here, 67 CD patients were analyzed; 43 (64%) were men. The median age (range) of onset was 25.6 (3-57) years. The median disease duration (range) was 7.6 (0-27) years. B1, B2, and B3 of Montreal Classification were established in 31 (46.2%), 21 (31.3%), and 15 (22.3%) patients, respectively. The median (range) of LRG was 21.7 (7.6-67.4) μg/mL. The median (range) of CRP was 10.8 (0.0-86.9) mg/L. LRG and CRP were strongly correlated (r=0.878, p<0.001). The ROC-AUC of LRG for mucosal healing was 0.839 (95% confidence interval [CI] 0.760-0.918). LRG cutoff value for discriminating mucosal healing was 15.5 μg/mL (sensitivity 77%, specificity 75%). The ROC-AUC of CRP for mucosal healing was 0.811 (95% CI 0.721-0.900). The CRP cutoff value to differentiate mucosal healing was 0.9 mg/L (sensitivity 55%, specificity 90%). 2) Forty CRP-negative CD patients were analyzed; 23 (57%) were men. The median age (range) of onset was 21.9 (3-57) years. The median disease duration (range) was 7.0 (0-27) years. B1, B2, and B3 of Montreal Classification were established in 17 (42.5%), 12 (30.0%), and 11 (27.5%) patients, respectively. The median (range) of LRG was 12.3 (7.6-23.5) μg/mL. The ROC-AUC of LRG for mucosal healing was 0.817 (95% CI 0.696-0.938). The LRG cutoff value to differentiate mucosal healing was 14.1 μg/mL (sensitivity 61%, specificity 76%). CONCLUSION LRG may be a better biomarker than CRP for assessing endoscopic remission of the small intestinal mucosa in CD. In CRP-negative CD patients, LRG level of ≥14.1 μg/mL could indicate small intestinal ulcers.