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

Journal of Crohn s and Colitis, vol. 20

Abstract

Abstract 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.

Authors 11

1. Daniëlle M.H. Barendregt

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

2. Bastiaan Tuk

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

3. D H Hulleman-van Haaften

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

4. A Camman

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

5. B Calado

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

6. Meike H Grillmaier

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

7. Willem K. Smits

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

8. Michail Doukas

   Erasmus MC

   Affiliation as printed

   Department of Pathology, Erasmus University Medical Center , Rotterdam, 3000 CA,

9. Johanna C Escher

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

10. Lissy de Ridder Aachen Department of Pediatrics, Willem-Alexander Children's Hospital

    Leiden University Medical Center · Erasmus MC · Willem-Alexander Kinderziekenhuis · Erasmus MC - Sophia Children’s Hospital

    Affiliation as printed

    Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,

    Department of Pediatrics, Willem-Alexander Children’s Hospital, Leiden University Medical Center , Leiden, 2300 RC,

11. Janneke N Samsom

    Erasmus MC · Erasmus MC - Sophia Children’s Hospital

    Affiliation as printed

    Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital , Rotterdam, 3000 CA,