Serum inter-alpha-trypsin inhibitor heavy chain 4 in patients with inflammatory bowel disease: correlation with disease risk, inflammation, activity, and its variation after treatment

Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays vital roles in inflammatory and auto-immune diseases, but its correlations with disease risk and clinical features in inflammatory bowel disease (IBD) need further investigation. The present study intended to explore the correlation of ITIH4 with disease activity and inflammation, as well as its change after treatment in IBD patients. Totally, 40 active Crohn’s disease (A-CD) patients, 40 clinical-remission CD (R-CD) patients, 40 active ulcerative colitis (A-UC) patients, 40 clinical-remission UC (R-UC) patients, and 40 health controls (HCs) were enrolled. ITIH4 in serum was assessed by ELISA. ITIH4 was lower in A-CD, R-CD, A-UC, and R-UC patients than in HCs (P < 0.001). Notably, ITIH4 reduced in A-CD patients than in R-CD patients (P = 0.017), and in A-UC patients compared with R-UC patients (P = 0.010). Besides, in A-CD patients, ITIH4 negatively correlated with tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A, IL-1β, C-reactive protein (CRP), and clinical disease activity index score (all P < 0.05). In A-UC patients, ITIH4 negatively correlated with TNF-α, IL-17A, IL-1β, IL-6, CRP, and Mayo score (all P < 0.05). However, in R-CD and R-UC patients, these correlations were less obvious than in A-CD and A-UC patients. ITIH4 was increased after treatment (all P < 0.05), and its expression at W12 after treatment was higher in response patients compared with no response patients in A-CD (P = 0.022) and A-UC groups (P = 0.038). ITIH4 correlates with IBD susceptibility, active risk, inflammation level, and its elevation after treatment relates to clinical response in IBD patients.