Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease

doi:10.3748/wjg.v27.i9.866

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World Journal of Gastroenterology

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World J Gastroenterol. Mar 7, 2021; 27(9): 866-885
Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.866

Table 1 Patient demographics and medical characteristics

Parameters	Controls (n = 82)	Crohn’s disease (n = 115)	Ulcerative colitis (n = 51)
Women	57 (69.5%)	58 (50.4%)	27 (52.9%)
Age (yr), median (IQR)	51.5 (36.5-60)	42 (28-58)	44 (37-56)
Disease duration (yr), median (IQR)		6 (3-11)	9 (3-14)
Age at diagnosis (yr)
A1; A2; A3, n (%)		10 (8.7); 57 (49.6); 48 (41.7)	8 (15.7); 29 (56.9); 14 (27.5)
Disease behavior
B1; B2; B3, n (%)		53 (46.1); 20 (17.4); 42 (36.5)	-
Disease location
L1; L2; L3/E1; E2; E3, n (%)		16 (13.9); 39 (33.9); 60 (52.2)	14 (27.5); 17 (33.3); 20 (39.2)
Perianal disease		23 (20.0%)	-
EIM		12 (10.4%)	3 (5.9%)
PSC		6 (5.2%)	5 (9.8%)
Previous surgery		36 (31.3%)	2 (3.9%)
Medical therapy
Biologicals		38 (33.0%)	5 (9.8%)
Immunosuppressants		66 (57.4%)	22 (43.1%)
Steroids		17 (14.8%)	3 (5.9%)
Salicylates		18 (15.7%)	26 (51.0%)
Clinically active		60 (52.2%)	33 (64.7%)
Endoscopically active		77 (66.9%)	35 (68.6%)
Histologically active		33/71 (46.5%)	9/29 (31.0%)
CRP, mg/L	1.65 (1.4-6.0)	2.8 (1.6-8.1)	4.3 (2.0-7.6)
ESR, mm/h	22 (10-30)	22 (10-42)	35 (19-67)
Fecal calprotectin, µg/g	122 (45-201)	199 (52-325)	218 (115-370)
Beta-glucan, µg/mL	17 (8-33)	35 (17-74)	23 (9-54)

The values are presented as numbers (percentages) or medians interquartile range; age at diagnosis: A1, < 17; A2, 17-40; A3, > 40; Disease behavior in Crohn’s disease: B1: Inflammatory; B2: Fibrostenosing; B3: Penetrating; Disease location in Crohn’s disease: L1: Ileal; L2: Colonic; L3: Ileo-colonic; Disease location in ulcerative colitis: E1: Proctitis; E2: Left sided colitis; E3: Extensive colitis; EIM: Extraintestinal manifestations; PSC: Primary sclerosing cholangitis; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 2 Performance analysis of different cutoff values of serum beta-glucan for patients with Crohn’s disease in relation to endoscopic and histological criteria

Predicted outcome		Cutoff	Sensitivity	Specificity	PPV	NPV	Accuracy
Endoscopic inflammation	Beta-glucan	40	50.0 (39.0-61.0)	71.8 (56.2-83.5)	77.5 (64.1-87.0)	42.4 (31.2-54.4)	57.4 (48.3-66.0)
	(μg/mL)	60	34.2 (24.5-45.4)	87.2 (73.3-94.4)	83.9 (67.4-92.9)	40.5 (30.6-51.2)	52.2 (43.1-61.1)
	Calprotectin	100	75.0 (56.6-87.3)	53.3 (30.1-75.2)	75.0 (56.6-87.3)	53.3 (30.1-75.2)	67.4 (52.5-79.5)
	(μg/g)	200	53.6 (35.8-70.5)	66.7 (41.7-84.8)	75.0 (53.1-88.8)	43.5 (25.6-63.2)	58.1 (43.3-71.6)
	CRP	3	49.2 (37.1-61.4)	50.0 (31.4-68.6)	71.4 (56.4-82.8)	27.9 (16.7-42.7)	49.4 (39.0-59.8)
	(mg/L)	5	34.4 (23.7-46.9)	66.7 (46.7-82.0)	72.4 (54.3-85.3)	28.6 (18.4-41.5)	43.5 (33.5-54.1)
Histological inflammation	Beta-glucan	40	78.8 (62.2-89.3)	60.5 (44.7-74.4)	63.4 (48.1-76.4)	76.7 (59.1-88.2)	69.0 (57.5-78.6)
	(μg/mL)	60	57.6 (40.8-72.8)	76.3 (60.8-87.0)	67.9 (49.3-82.1)	67.5 (52.5-79.5)	67.6 (56.1-77.3)
	Calprotectin	100	69.2 (42.4-87.3)	41.7 (19.3-68.0)	56.2 (33.2-76.9)	55.6 (26.7-81.1)	56.0 (37.1-73.3)
	(μg/g)	200	46.1 (23.2-70.9)	50.0 (25.4-74.6)	50.0 (25.4-74.6)	46.1 (23.2-70.9)	48.0 (30.0-66.5)
	CRP	3	57.7 (38.9-74.5)	62.1 (44.0-77.3)	57.7 (38.9-74.5)	62.1 (44.0-77.3)	60.0 (46.8-71.9)
	(mg/L)	5	53.8 (35.5-71.2)	79.3 (61.6-90.1)	70.0 (48.1-85.4)	65.7 (49.1-79.2)	67.3 (54.1-78.2)

Endoscopic criteria based on the Simple Endoscopic Score-Crohn’s disease endoscopic subscore; Histological criteria based on a modified Global Histologic disease activity score; Parentheses show lower-upper 95% confidence interval. CRP: C-reactive protein; PPV: Positive predictive value; NPV: Negative predictive value.

Table 3 Performance analysis of different cutoff values of serum beta-glucan for patients with ulcerative colitis in relation to endoscopic and histological criteria

Predicted outcome		Cutoff	Sensitivity	Specificity	PPV	NPV	Accuracy
Endoscopic inflammation	Beta-glucan	40	40.0 (25.6-56.4)	87.5 (64.0-96.5)	87.5 (64.0-96.5)	40.0 (25.6-56.4)	54.9 (41.4-67.7)
	(μg/mL)	60	22.9 (12.1-39.0)	87.5 (64.0-96.5)	80.0 (49.0-94.3)	34.1 (21.6-49.4)	43.1 (30.5-56.7)
	Calprotectin	100	81.2 (57.0-93.4)	20.0 (3.6-62.4)	76.5 (52.7-90.4)	25.0 (4.6-69.9)	66.7 (45.4-82.8)
	(μg/g)	200	62.5 (38.6-81.5)	80.0 (37.5-96.4)	90.9 (62.3-98.4)	40.0 (16.8-68.7)	66.7 (45.4-82.8)
	CRP	3	60.9 (40.8-77.8)	20.0 (5.7-51.0)	63.7 (42.9-80.3)	18.2 (5.1-47.7)	48.5 (32.5-64.8)
	(mg/L)	5	43.5 (25.6-63.2)	60.0 (31.3-83.2)	71.4 (45.3-88.3)	31.6 (15.4-54.0)	48.5 (32.5-64.8)
Histological inflammation	Beta-glucan	40	66.7 (35.4-87.9)	90.0 (69.9-97.2)	75.0 (40.9-92.8)	85.7 (65.4-95.0)	82.8 (65.5-92.4)
	(μg/mL)	60	55.6 (26.7-81.1)	95.0 (76.4-99.1)	83.3 (43.6-97.0)	82.6 (62.9-93.0)	82.8 (65.5-92.4)
	Calprotectin	100	100.0 (64.6-100.0)	25.0 (7.1-59.1)	53.8 (29.1-76.8)	100.0 (34.2-100.0)	60.0 (35.7-80.2)
	(μg/g)	200	85.7 (48.7-97.4)	50.0 (21.5-78.5)	60.0 (31.3-83.2)	80.0 (37.5-96.4)	66.7 (41.7-84.8)
	CRP	3	57.1 (25.0-84.2)	33.3 (13.8-60.9)	33.3 (13.8-60.9)	57.1 (25.0-84.2)	42.1 (23.1-63.7)
	(mg/L)	5	42.9 (15.8-74.9)	58.3 (31.9-80.7)	37.5 (13.7-69.4)	63.6 (35.4-84.8)	52.6 (31.7-72.7)

Endoscopic criteria based on the Mayo endoscopic subscore; Histological criteria based on the Geboes score. Parentheses show lower-upper 95% confidence interval. CRP: C-reactive protein; PPV: Positive predictive value; NPV: Negative predictive value.

Table 4 Patient demographics and medical characteristics of the subgroup for the analysis of noninvasive markers

Parameters	Control group (n = 15)	Crohn’s disease group (n = 28)	Ulcerative colitis group (n = 25)	P value
Women, n (%)	11 (73)	12 (43)	16 (64)	0.110
Age (yr), median (IQR)	57 (37-63)	36 (26-58)	41 (33-56)	0.158
Disease duration (yr), median (IQR)		6 (2-12.5)	9 (3-10.5)	0.521
Age at diagnosis (yr)
A1; A2; A3, n (%)		3 (11); 14 (50); 11 (39)	5 (20); 15 (60); 5 (20)	0.269
Disease behavior
B1; B2; B3, n (%)		16 (57); 4 (14); 8 (29)	-	-
Disease location
L1; L2; L3/E1; E2; E3, n (%)		5 (18); 9 (32); 14 (50)	5 (20); 12 (48); 8 (32)	-
Perianal disease, n (%)		5 (18)	-	-
EIM, n (%)		4 (14)	2 (8)	0.391
PSC, n (%)		1 (3.6)	3 (12)	0.263
Previous surgery, n (%)		9 (32)	1 (4.0)	0.010
Medical therapy, n (%)
Biologicals		10 (36)	2 (8.0)	0.017
Immunosuppressants		18 (64)	5 (20)	0.001
Steroids		8 (29)	1 (4.0)	0.019
Salicylates		6 (21)	14 (56)	0.010
Clinically active, n (%)		13 (46)	21 (84)	0.005
Endoscopically active, n (%)		23 (82)	17 (68)	0.191
Histologically active, n (%)		14/22 (64)	4/14 (29)	0.043
Beta-glucan, µg/mL	26 (8-43)	79 (30-183)	23 (9-69)	0.0003^a
LBP, pg/mL	19.2 (16.4-22.7)	27.3 (24.3-28.6)	21.8 (19.8-24.6)	0.002^b
Zonulin, pg/mL	16.4 (15.3-17.1)	17.6 (16.6-19.0)	17.2 (16.6-18.7)	0.09
IL-17 (10²), pg/mL	0.04 (0.0-1.50)	0.08 (0.0-1.75)	0.00 (0.00-0.60)	0.2479
IFN-gamma, pg/mL	0.00 (0.00-0.690)	0.021 (0.00-0.66)	0.25 (0.001-0.92)	0.5276
TNF-alpha (10²), pg/mL	0.00 (0.00-1.00)	0.10 (0.00-7.80)	0.00 (0.00-20.01)	0.9004
IL-10, pg/mL	0.00 (0.00-0.00)	0.00 (0.00-4.56)	1.35 (0.00-3.66)	0.4801
IL-6, pg/mL	3.27 (2.38-9.05)	5.70 (0.31-35.73)	4.35 (2.28-15.91)	0.4149
IL-4, pg/mL	0.055 (0.00-6.81)	0.00 (0.00-0.087)	0.00 (0.00-1.31)	0.2597
IL-2, pg/mL	0.00 (0.00-0.052)	0.00 (0.00-0.010)	0.00 (0.00-0.04)	0.9204

In pairwise comparisons:

^a,bCrohn’s disease > Control. Values are presented as number (percentage) or median (IQR: Interquartile range); age at diagnosis: A1, < 17; A2, 17-40; A3, > 40; Disease behavior in Crohn’s disease: B1: Inflammatory; B2: Fibrostenosing; B3: Penetrating; Disease location in Crohn’s disease: L1: Ileal; L2: Colonic; L3: Ileo-colonic; Disease location in ulcerative colitis: E1: Proctitis; E2: Left sided colitis; E3: Extensive colitis; EIM: Extraintestinal manifestations; PSC: Primary sclerosing cholangitis; LBP: Lipopolysaccharide-binding protein.

Citation: Farias e Silva K, Nanini HF, Cascabulho CM, Rosas SLB, Santana PT, Carneiro AJV, Anaissie E, Nucci M, de Souza HSP. Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease. World J Gastroenterol 2021; 27(9): 866-885
URL: https://www.wjgnet.com/1007-9327/full/v27/i9/866.htm
DOI: https://dx.doi.org/10.3748/wjg.v27.i9.866