Intest Res.  2024 Oct;22(4):473-483. 10.5217/ir.2023.00135.

Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis

• Karashima R
• Sagami S
• Yamana Y
• Maeda M
• Hojo A
• Miyatani Y
• Nakano M
• Matsuda T
• Hibi T
• Kobayashi T

• KMID: 2560297
• DOI: http://doi.org/10.5217/ir.2023.00135

Abstract

Background/Aims
Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated.
Methods
Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed.
Results
A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8.
Conclusions
LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.

Keyword

Leucine-rich α-2-glycoprotein; Inflammatory bowel disease; Ulcerative colitis; Biomarkers

Figure

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  Fig. 1. Patient disposition of the study. MES, Mayo endoscopic subscore.

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  Fig. 2. Correlation between biomarkers using Spearman’s rank correlation coefficient. (A) Correlation between LRG and CRP. (B) Correlation between FC and LRG. (C) Correlation between CRP and FC. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin.

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  Fig. 3. Changes of biomarkers in response to treatment in ulcerative colitis patients after initiation of induction therapy are shown: values of (A) LRG, (B) CRP, and (C) FC in patients in remission and non-remission groups at week 8 are shown as mean±standard deviation and compared at each time point using the Wilcoxon matched-pairs signedrank test. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin.

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  Fig. 4. Comparison of (A) LRG, (B) CRP, and (C) FC at week 1 in the remission and non-remission groups at week 8. Statistical significance was determined by Wilcoxon signed-rank test. Receiver operating characteristic curve analysis of (D) LRG, (E) CRP, and (F) FC at week 1 for clinical remission at week 8. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin; AUC, area under the curve.

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  Fig. 5. Comparison of (A) LRG, (B) CRP, and (C) FC at week 1 in the remission and non-remission groups at week 8, limited to patients who were not in remission at week 1 after starting induction therapy. Statistical significance was determined by Wilcoxon signed-rank test. Receiver operating characteristic curve analysis of (D) LRG, (E) CRP, and (F) FC at week 1 for clinical remission at week 8 in patients not in clinical remission at week 1. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin; AUC, area under the curve.

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  Fig. 6. Comparison of (A) LRG, (B) CRP, and (C) FC at week 1 in the remission and non-remission groups at week 8, limited to severe ulcerative colitis with partial Mayo score 7 or above at baseline. Statistical significance was determined by Wilcoxon signed-rank test. Receiver operating characteristic curve analysis of (D) LRG, (E) CRP, and (F) FC at week 1 for clinical remission at week 8 in patients not in clinical remission at week 1. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin; AUC, area under the curve.

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  Fig. 7. Comparison of (A) LRG, (B) CRP, and (C) FC at week 1 in the endoscopic improvement and non-endoscopic improvement groups for endoscopies performed within 1 year. Statistical significance was determined by Wilcoxon signed-rank test. Receiver operating characteristic curve analysis of (D) LRG, (E) CRP, and (F) FC at week 1 for endoscopic improvement within 1 year. LRG, leucine-rich α-2- glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin; AUC, area under the curve.

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  Fig. 8. Comparison of (A) LRG, (B) CRP, and (C) FC at week 1 in the endoscopic improvement and non-endoscopic improvement groups for endoscopies performed within 1 year, limited to severe ulcerative colitis with partial Mayo score 7 or above at baseline. Statistical significance was determined by Wilcoxon signed-rank test. Receiver operating characteristic curve analysis of (D) LRG, (E) CRP, and (F) FC at week 1 for endoscopic improvement within 1 year. LRG, leucine-rich α-2-glycoprotein; CRP, C-reactive protein; FC, fecal calprotectin; AUC, area under the curve.

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