Role of leucine-rich α-2-glycoprotein in Taiwanese patients with inflammatory bowel disease as a predictive biomarker for endoscopic activity

Table 1 Clinical characteristics of patients with inflammatory bowel disease, n (%)

	UC (n = 100)	CD (n = 103)
Male sex	54 (54.0)	69 (67.0)
Age (years old), median (IQR)	50 (40-61)	43 (33-56)
Time interval, day, median (IQR)1	11.5 (3-24)	15.5 (6.5-24)
Disease extent
E1	2 (2.0)	-
E2	16 (16.0)	-
E3	82 (82.0)	-
L1	-	2 (1.9)
L2	-	11 (10.7)
L3	-	90 (87.4)
Upper GI modifier	-	5 (4.9)
Perianal disease modifier	-	14 (13.6)
Laboratory data, median (IQR)
Hb (g/dL)	13.5 (12.5-14.5)	13.9 (12.6-15)
Alb (g/dL)	4.5 (4.3-4.7)	4.5 (4.4-4.8)
CRP (mg/dL)	0.1 (0.05-0.23)	0.11 (0.05-0.33)
LRG (μg/mL)	8.6 (7.05-11.1)	9.0 (6.9-12.1)
FC (mg/kg)	47.5 (17-230)	68 (32-257)
Endoscopic activity
MES < 2	51 (51)	-
MES ≥ 2	49 (49)	-
SES-CD < 6	-	76 (73.8)
SES-CD ≥ 6	-	27 (26.2)
Clinical disease activity, median (IQR)
Partial Mayo score	0 (0-1)	-
HBI	-	1 (0-2)
Medications
No current therapies	3 (3.0)	8 (7.8)
5-ASA	91 (91.0)	15 (14.6)
Immunomodulators	16 (16.0)	57 (55.3)
Corticosteroid	9 (9.0)	3 (2.9)
Biologics
Anti-TNF	2 (2.0)	40 (38.8)
Anti-integrin	17 (17.0)	5 (4.9)
Anti-IL12/23 or anti-IL23	5 (5.0)	19 (18.4)
JAK inhibitor	9 (9.0)	1 (1.0)

¹Time interval (days) between endoscopy and laboratory tests.

UC: Ulcerative colitis; CD: Crohn’s disease; IQR: Interquartile range; E1: Proctitis; E2: Left-sided; E3: Extensive disease; L1: Ileal; L2: Colonic; L3: Ileocolonic; GI: Gastrointestinal; Hb: Hemoglobin; Alb: Albumin; CRP: C-reactive protein; LRG: Leucine-rich α-2-glycoprotein; FC: Fecal calprotectin; MES: Mayo endoscopic subscore; SES-CD: Simple Endoscopic Score for Crohn’s disease; HBI: Harvey-Bradshaw index; 5-ASA: 5-aminosalicylic acid; TNF: Tumor necrosis factor; IL: Interleukin; JAK: Janus kinase.

Table 2 Correlation of leucine-rich α-2-glycoprotein with other biomarkers

			CRP	Alb	Hb	FC
IBD	Correlation coefficient	LRG	0.565	-0.484	-0.479	0.155
	Two-tailed significance		< 0.001	< 0.001	< 0.001	0.028
UC	Correlation coefficient	LRG	0.376	-0.358	-0.489	0.201
	Two-tailed significance		< 0.001	< 0.001	< 0.001	0.045
CD	Correlation coefficient	LRG	0.629	-0.584	-0.495	0.179
	Two-tailed significance		< 0.001	< 0.001	< 0.001	0.07

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; LRG: Leucine-rich α-2-glycoprotein; CRP: C-reactive protein; Alb: Albumin; Hb: Hemoglobin; FC: Fecal calprotectin.

Table 3 Comparison of biomarkers between endoscopically active and inactive groups, median (interquartile range)

	Active	Inactive	P value
IBD
LRG, μg/mL	9.5 (7.25-11.75)	8.5 (6.75-11.2)	0.049a
CRP, mg/dL	0.13 (0.06-0.33)	0.08 (0.04-0.23)	0.079
Hb, g/dL	13.9 (12.6-15.0)	13.7 (12.5-14.6)	0.403
Alb, g/dL	4.5 (4.3-4.7)	4.5 (4.4-4.8)	0.582
FC, mg/kg	217 (45-880)	47 (18-132)	< 0.001a
UC
LRG, μg/mL	8.8 (7.5-11.2)	8.3 (6.7-11)	0.431
CRP, mg/dL	0.11 (0.05-0.23)	0.08 (0.05-0.21)	0.815
Hb, g/dL	14 (12.8-14.8)	13.3 (12.4-14.5)	0.221
Alb, g/dL	4.6 (4.3-4.8)	4.5 (4.4-4.7)	0.905
FC, mg/kg	102 (45-1336)	31 (10-79.5)	0.006a
CD
LRG, μg/mL	11 (7-16.5)	8.6 (6.9-11.4)	0.012a
CRP, mg/dL	0.2 (0.1-0.65)	0.09 (0.04-0.23)	0.019a
Hb, g/dL	14.3 (12.2-15.5)	13.9 (12.8-14.6)	0.753
Alb, g/dL	4.5 (4.4-4.6)	4.5 (4.4-4.8)	0.269
FC, mg/kg	273 (55-626)	57.5 (27-167)	< 0.001a

^aP < 0.05.

IBD: Inflammatory bowel disease; LRG: Leucine-rich α-2-glycoprotein; CRP: C-reactive protein; Hb: Hemoglobin; Alb: Albumin; FC: Fecal calprotectin; UC: Ulcerative colitis; CD: Crohn’s disease.

Table 4 Summary of previous and current studies using leucine-rich α-2-glycoprotein to predict inflammatory bowel disease activity

Reference	Endpoints/AUC	Sensitivity/specificity	Cutoff for LRG
Serada et al[6], 2012	UC/clinical CAI
LRG, μg/mL	0.901	84.0%/82.5%	7.21
CRP, mg/dL	0.845	80.0%/80.7%	0.20
Takenaka et al[17], 2023	CD/transmural inflammation
LRG, μg/mL	0.845	67%/90%	14
CRP, mg/dL	0.766	48%/94%	0.03
Asonuma et al[12], 2023	CD/small bowel lesions
LRG, μg/mL	0.77	89.0%/100%	9/16
CRP, mg/dL	0.74	50%/89%	1
Shimoyama et al[16], 2023	IBD/MES > 0 or SES-CD > 2
LRG (UC), μg/mL	0.80	71%/85%	12.7
CRP (UC), mg/dL	0.72	56%/80%	0.14
LRG (CD), μg/mL	0.79	88%/63%	13.3
CRP (CD), mg/dL	0.78	65%/75%	0.46
	IBD/partial Mayo > 0/CDAI > 150
LRG (UC), μg/mL	0.73	69%/73%	12.7
CRP (UC), mg/dL	0.63	66%/53%	0.08
LRG (CD), μg/mL	0.71	67%/71%	22.2
CRP (CD), mg/dL	0.64	64%/68%	0.9
Takada et al[28], 2025	CD/SES-CD > 6
LRG, μg/mL	0.74	70.8%/87.5%	15.5
CRP, mg/dL	0.63	58.3%/71.9%	0.13
Aoyama et al[29], 2025	UC/MES > 1
LRG, μg/mL	0.68	50%/82%	14.8
CRP, mg/dL	0.62	44%/83%	0.21
Ojaghi Shirmard et al[23], 2025	IBD/meta-analysis
LRG, μg/mL	0.82	75.4%/77.3%	-
Current study	IBD/MES ≥ 2 for UC, SES-CD ≥ 6
LRG (UC), μg/mL	0.57	69%/50%	8.1
CRP (UC), mg/dL	0.45	98%/6%	1.01
LRG (CD), μg/mL	0.61	59%/70%	10.8
CRP (CD), mg/dL	0.70	85%/46%	0.08

AUC: Area under the curve; LRG: Leucine-rich α-2-glycoprotein; UC: Ulcerative colitis; CAI: Clinical activity index; CRP: C-reactive protein; CD: Crohn’s disease; IBD: Inflammatory bowel disease; MES: Mayo endoscopic subscore; SES-CD: Simple Endoscopic Score for Crohn’s disease; CDAI: Crohn’s disease activity index.