328 Severe disease (>16) 3 (4.4) 2 (7.1) 0 (0.0) 1 (5.6) Laboratory parameters - Hemoglobin (mmol/L) 7.7 ± 0.9 7.8 ± 1.0 7.9 ± 0.9 7.6 ± 0.9 0.349 CRP (mg/L) 5.0 [2.1;14.8] 9.6 [4.2;17.8] 2.0 [1.0;5.7] 6.2 [3.2;15.5] 0.003 WBC (x109/L) 7.1 [6.9;9.8] 8.5 [6.5;11.3] 6.4 [4.9;9.2] 6.8 [6.0;9.1] 0.085 Platelets (x109/L) 334 ± 102 366 ± 107 289 ± 82 337 ± 99 0.010 eGFR (mL/min/1.73 m2) 106 ± 23 109 ± 20 108 ± 30 102 ± 20 0.400 Creatinine (μmol/L) 66.2 ± 15.1 63.1 ± 13.7 66.4 ± 18.1 69.1 ± 13.8 0.238 Faecal calprotectin (μg/g)^ 1105 [553;2185] 1895 [1170;2473] 625 [425;805] 865 [400;1490] 0.010 Data are presented as proportions n with corresponding percentages (%), means ± standard deviation (SD) or medians [interquartile range, IQR] in case of continuous variables. P-values < 0.05were considered statistically significant. †Clinical disease activity scores (HBI) were available for n = 68 patients. ^Fecal calprotectin levels at baseline were available for n = 38 patients (B1: n=16; B2: n=11; B3: n=11). BMI, body-mass index; CD, Crohn’s disease; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; HBI, Harvey Bradshaw Index; HC, healthy controls; TNF-α, tumor necrosis factor alpha; WBC, white blood cell count. CD is characterized by distinct biomarker signatures of type I, III, IV, and VI collagen formation and degradation Serum concentrations of type I, III, IV, and VI collagen formation and degradation biomarkers in patients with CD and in healthy controls (HC) are presented in Table S2 and separated out according to Montreal classification in Figure 2. Serum levels of C1M and C6Ma3 were substantially elevated in patients with CD compared with healthy controls (C1M: 50.6[33.9;105.7] vs. 14.3[11.4;19.9] ng/mL; C6Ma3: 0.62[0.49;0.84] vs. 0.44[0.41;0.47] ng/mL, both P<0.001, Table S2). No significant differences in serum C1M (after adjustment for multiple comparisons) and C6Ma3 levels were observed between disease behavior subclasses (i.e., without considering HC), although patients with stricturing disease showed a trend towards lower levels than the remaining patients. Serum C3M levels were significantly elevated in patients with CD compared with healthy controls (median [IQR] 11.8[9.7;14.6] vs. 9.2[7.8;10.4] ng/mL, P<0.001), indicating relatively increased degradation of type III collagen, whereas PRO-C3 levels were not significantly different between groups (nominal P-value: 0.029) (Table S2). Taken together, the balance between type III collagen formation and degradation (C3M/PRO-C3 ratio) was higher in patients with non-stricturing, non-penetrating CD (Montreal B1) compared with healthy controls (albeit only nominally significant, P=0.010; Table S2). Serum PRO-C4 and C4M levels were higher in patients with CD than in healthy controls (183.3[144.7;239.1] vs. 134.2[105.2;160.1] ng/mL and 26.3[22.6;34.5] vs. 21.1[18.1;24.7] ng/mL, both P<0.001) (Table S2). However, the balance between type IV collagen formation and degradation (PRO-C4/C4M ratio) was not significantly elevated in patients with stricturing CD (Montreal B2), compared with healthy controls or patients with CD having non-stricturing, non-penetrating disease (B1) and penetrating disease (B3) (P=0.153 and P=0.009, respectively). Serum C4G levels were higher in patients with penetrating CD compared with healthy controls (18.0 [14.0;26.3] vs. 13.7[10.7;19.6] ng/mL, respectively, overall P=0.006), indicating net increased T-cell granzyme-B-mediated degradation of type IV collagen, although there was no statistically significant difference between disease behavior phenotypes. Chapter 10
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