Serum Lipopolysaccharide-binding Protein and Soluble CD14 Are Markers of Disease Activity in Patients with Crohn's Disease

Background: In inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. In the present study we investigated the association between serum level of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and clinical disease activity, high-sensitivity C-reactive protein (hs-CRP), antimicrobial serology profile, NOD2/CARD15 status, and clinical phenotype in a large cohort of Hungarian Crohn's disease (CD) patients. Methods: In all, 214 well-characterized, unrelated, consecutive CD patients (male/female ratio: 95/119; age: 35.6 +/- 13.1 years; duration:8.3 +/- 7.5 years) and 110 healthy controls were investigated. Sera were assayed for LBP, sCD14, hs-CRP, ASCA IgG/IgA, anti-OMP IgA, and pANCA antibodies. NOD2/CARD15 and TLR4 variants were tested. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. Results: Serum LBP level was significantly higher (P < 0.0001 for both), while sCD14 was lower (P < 0.0001) in both active and inactive CD compared to the controls. The accuracy of hs-CRP (area under the curve [AUC] = 0.66), sCD14 (AUC = 0.70), and LBP (AUC = 0.58) was comparable for identifying patients with active disease. There was a significant correlation between LBP (P < 0.001), sCD14 (P = 0.015), and hs-CRP levels but not with antimicrobial seroreactivity or NOD2/CARD15 genotype. In inactive CD, LBP was associated with penetrating disease. In a Kaplan-Meier analysis and a proportional Cox-regression analysis, LBP (P = 0.006), sCD14 (P = 0.007), and previous relapse frequency (P = 0.023) were independently associated with time to clinical relapse during a 12-month follow-up period. Conclusions: Serum LBP and sCD14 are markers of disease activity in CD with a similar accuracy as hs-CRP. In addition, LBP, sCD14, and a high frequency of previous relapses were independent predictors for 1-year clinical flare-up.