Higher plasma levels of lipopolysaccharide-binding protein (LBP) were significantly associated with increased risk of surgery (HR 2.15) and stenosis (HR 2.00) in IBD patients.
Do blood-based biomarkers of gut barrier integrity (FABP2, LBP, sCD14) associate with disease activity and predict future disease progression in patients with inflammatory bowel disease?
Elevated plasma levels of LBP and sCD14 are associated with clinical and endoscopic disease activity and prospectively predict the risk of surgery and stenosis in patients with inflammatory bowel disease.
Absolute Event Rate: 0% vs 0%
Abstract Background Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), involves impaired intestinal barrier function, which can precede symptoms and predict adverse outcomes. Blood-based biomarkers reflecting epithelial damage or microbial exposure may aid disease monitoring. This study evaluated fatty acid-binding protein 2 (FABP2), lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14) as markers of disease activity and disease progression in two independent IBD cohorts. Methods This study featured two IBD cohorts; the first cohort included 1,009 patients with IBD (562 CD, 447 UC), and 480 healthy controls, with comprehensive clinical and biochemical characterization and longitudinal follow-up. Disease progression was defined as the risk of requiring IBD-related surgery or the development of intestinal stenosis. The second cohort included 111 patients (46 CD, 65 UC) with parallel data on endoscopic disease activity as quantified by the Simple Endoscopic Score and Mayo endoscopic subscore. Plasma levels of FABP2, LBP, and sCD14 were measured using ELISA. Clinical disease activity was assessed using Simple Clinical Colitis Activity Index and Harvey-Bradshaw Index, and biochemical disease activity by C-reactive protein (CRP). Results LBP was higher in both clinically (p 0.05) and biochemically active IBD (p 0.05) (Fig. 1A-B). On multivariable analysis, both sCD14 and LBP levels were elevated in patients with severe endoscopic disease activity compared with patients in endoscopic remission (Fig 1C-D) (p 0.05). During a median follow-up of 9.6 IQR: 7.1–12.3 years, 213 (21.1%) (CD: 151, UC: 62) patients underwent surgery and 168 (16.7%) (CD: 168) patients developed stenosis. On multivariable analysis, adjusting for age, sex, smoking status, age of onset, and medication use, higher LBP levels were significantly associated with an increased risk of surgery (HR per doubling: 2.15 1.68-2.77, p 0.05, Fig. 2A-B) and stenosis for the entire cohort (HR per doubling: 2.00 1.52-2.62, p 0.05) (Fig. 2C-D). FABP2 was not significantly associated with any cross-sectional or future disease outcomes. Conclusion This study supports the hypothesis that impaired intestinal barrier function, reflected by elevated plasma levels of sCD14 and LBP, is significantly associated with clinical, biochemical and endoscopic disease activity and prospectively associated with disease progression in patients with IBD. These findings indicate that LBP, and potentially sCD14, could serve as valuable biomarkers for disease monitoring, risk stratification, and potentially guide therapeutic interventions in IBD management. Conflict of interest: Mr. Geertsema, Sem: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Bourgonje, Arno R.: A.R.B. received speaker’s fees from AbbVie and Ferring, outside the submitted work. This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Veenstra, Fokkelien: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Gacesa, Ranko: Grant: Partially funded by Janssen Pharmaceuticals (for projects unrelated to any of research presented at this conference) Personal Fees: Paid freelance consulting for Esox biologicals ltd. (for projects unrelated to any of research presented at this conference) Fagundes, Raphael R.: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Spekhorst, Lieke: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Hu, Shixian: Grant: Chinese Government de Jong, Sofie: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Jansen, Bernadien H.: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Holstein, Hannah: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Ruane, Darren: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Kannan, Arun K: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Weersma, Rinse K: R.K.W. acted as consultant for Takeda Pharmaceuticals received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico and Ferring and received speaker’s fees from MSD, Abbvie and Janssen Pharmaceuticals. This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. van Goor, Harry: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. Dijkstra, Gerard: Grant: Royal DSM Personal Fees: Consultancy fee from Astra-Zeneca and Speakers fee from Abbvie Faber, Klaas-Nico: This study was supported by Janssen Research & Development LLC. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results.
Geertsema et al. (Thu,) reported a other. Higher plasma levels of lipopolysaccharide-binding protein (LBP) were significantly associated with increased risk of surgery (HR 2.15) and stenosis (HR 2.00) in IBD patients.