Plasma lipopolysaccharide-binding protein (LBP), a proxy for intestinal permeability, relates to clinicopathological and immunological disease activity in inflammatory bowel disease patients at diagnosis and during disease course.

BACKGROUND AND AIMS: Intestinal barrier healing is the treatment goal in ulcerative colitis (UC) and Crohn's disease (CD). Despite this, systematic analyses of the relationship between intestinal permeability and clinicopathological and immunological disease activity at diagnosis and during follow-up are lacking. Therefore, we assessed this relationship using plasma lipopolysaccharide-binding protein (LBP)-an indirect biomarker of systemic exposure to bacterial endotoxins-as a proxy for intestinal permeability, in a uniquely well-characterized pediatric inflammatory bowel disease (IBD) cohort.

METHODS

LBP was measured in 1083 longitudinal plasma samples of newly diagnosed pediatric UC (n = 61), CD (n = 115) (PIBD-SETQuality and TISKids prospective cohorts; median follow-up 628 days), and controls (IBD-negative, n = 33; healthy, n = 28). Its relationship with clinicopathological parameters and plasma immune proteomics was examined.

RESULTS

Plasma LBP was elevated and associated with clinicopathological disease activity in therapy-naive CD and UC. In UC, but not CD, LBP related to disease extent, and strongly and independently correlated to endoscopic and histological disease activity, providing additional explanatory value beyond routinely used blood-based biomarkers and inflammatory mediators (including CRP and IL-6). LBP correlated with disease-specific immune profiles linked to severe disease (IL-17/neutrophil/IFN-γ-related profile in UC; IFN-γ-related profile in CD). LBP decreased after induction therapy with corticosteroids in UC, and after exclusive enteral nutrition or anti-TNF (but not corticosteroids) in CD. LBP remained associated with clinicopathological disease activity during follow-up, particularly in UC.

CONCLUSIONS

Plasma LBP relates to clinicopathological and immunological disease activity in IBD-especially UC-at diagnosis and during follow-up, and provides complementary information to routinely used blood-based biomarkers, arguing this simple, inexpensive parameter should be (re)considered for monitoring mucosal inflammation in UC.