Soluble ST2: A new and promising activity marker in ulcerative colitis

Table 1 Clinical characteristics of the patient groups n (%)

	IBD						Controls
	UC				CD		Non-IBD	HC
No. of patients	84				26		43	40
Female (%)	48 (57.1)				13 (50)		23 (53.4)	18 (45)
Age (mean ± SD, yr)	38 ± 12.6				42.6 ± 15.5		49.8 ± 18.3	30.8 ± 5.4
Location of disease
Ulcerative proctitis, E1	16 (19)
Left-sided colitis, E2	16 (19)
Extensive colitis, E3	52 (62)
Small bowel, L1					4 (15.5)
Colon, L2					15 (57.6)
Ileocolonic, L3					7 (26.9)
Disease behavior
Inflammatory					25 (96.1)
Stenosing					1 (3.9)
Penetrating					0
Index disease	0	1	2	3	≤ 8	≥ 9
Endoscopic Mayo score	8 (9.5)	40 (47.6)	25 (29.7)	11(13.2)
Histopathological score	8 (9.5)	35 (41.6)	32 (38.1)	9 (10.7)
Harvey-Bradshaw Index					22 (84.6)	4 (15.4)
SES-CD					24 (92.3)	2 (7.7)
Medication at endoscopy
No medication	14 (16.6)				5 (19.2)
Topical 5-ASA	16 (19)				2 (7.7)
Systemic 5-ASA	24 (28.5)				7 (26.9)
Systemic steroids	10 (11.9)				3 (11.6)
5-ASA + steroids	13 (15.5)				0
5-ASA + azathioprine	7 (8.5)				4 (15.4)
Azathioprine	0				5 (19.2)

Data regarding location of disease, disease behavior, index disease and medication at endoscopy are represented as number of patients (%). UC: Ulcerative colitis; CD: Crohn’s disease; HC: Healthy subjects; SES-CD: Simplified endoscopic activity score for Crohn’s disease; 5-ASA: 5-aminosalicylic acid derivatives; IBD: Inflammatory bowel diseases.

Table 2 Sensitivity, specificity and cut-off values for sST2 in ulcerative colitis patients compared to other groups

	Inactive UC				Active UC
	Cut-off value (pg/mL)	Sensitivity (%)	Specificity (%)	AUC (95% CI)	Cut-off value (pg/mL)	Sensitivity (%)	Specificity (%)	AUC (95% CI)
HC	33.08	54.29	52.08	0.58 (0.46 -0.71)	64.25	94.29	91.67	0.98 (0.95-1.00)b
Non IBD	42.67	60.98	64.58	0.58 (0.45-0.70)	76.29	80.49	83.33	0.90 (0.84-0.97)b
iUC	-	-	-	-	74.87	83.33	83.33	0.92 (0.86-0.97)b

^bP < 0.0001. iUC: Inactive ulcerative colitis; HC: Healthy subjects; IBD: Inflammatory bowel disease; AUC: Area under the curve.

Table 3 Correlation data of endoscopic and histopathological scores with serum sST2, interleukin-33, interleukin-6, tumor necrosis factor-α levels and total intestinal ST2

Disease activity index	Endoscopic score	Histopathological score
sST2 (pg/mL)
r	0.7624	0.6762
P-value	< 0.0001	< 0.0001
IL-33 (pg/mL)
r	0.2869	0.1687
P-value	0.0146	0.1657
IL-6 (pg/mL)
r	0.2315	0.0888
P-value	0.0676	0.2855
TNF-α (pg/mL)
r	0.6961	0.6112
P-value	< 0.0001	< 0.0001
Intestinal ST2 (pg/mL per mg protein)
r	0.6267	0.6034
P-value	< 0.0001	< 0.0001

IL: Interleukin; TNF: Tumor necrosis factor; r: Spearman’s rank correlation coefficient.

Table 4 Baseline serum sST2 levels according to clinical characteristics of patients

	Serum sST2 (pg/mL), median (Percentiles 25th-75th)
	UC	Non-IBD	HC
Gender
Female	55.5 (29.3-150.1)	43.9 (22.1-73.1)	29.4 (17.0-40.3)
Male	99.7 (34.0-216.4)	59.7 (35.6-74.9)	36.2 (27.0-53.2)
Age (yr)
18-24	190.8 (52.6-489.6)	63.2 (31.7-74.9)	29.0 (17.0-45.0)
25-34	66.2 (30.4-313.3)	46.3 (18.5-116.6)	32.4 (16.9-40.8)
35-44	125.4 (37.0-182.9)	48.1 (32.2-67.8)	44.3 (27.9-59.6)
45-54	48.2 (24.9-116.4)	43.6 (26.0-72.4)	51.0 (35.7-65.0)
≥ 55	51.3 (19.9-90.5)	53.0 (25.9-78.8)	0
Location of disease
Ulcerative proctitis, E1	56.5 (22.4-141.6)
Left-sided colitis, E2	35.8 (19.4-66.2)
Extensive colitis, E3	110.2 (34.0-345.8)a
Medication at endoscopy
No medication	36.4 (19.6-105.6)
Topical 5-ASA	39.7 (20.4-75.7)
Systemic 5-ASA	59.0 (23.6-141.7)
Systemic steroids	242.4 (124.9-349.1)a
5-ASA + steroids	125.4 (50.0-417.9)
5-ASA + azathioprine	41.1 (68.9-109.0)
Azathioprine	0

^aP≤ 0.05 vs other groups in the analysis. UC: Ulcerative colitis; HC: Healthy subjects; IBD: Inflammatory bowel disease; 5-ASA: 5-aminosalicylic acid derivatives.