ECTRIMS eLearning

Patients with early MS and an altered intestinal barrier have a distinct immunologic phenotype
Author(s): ,
C. Camara
Affiliations:
Clinical Neurosciences | MS Clinic
,
J. Hahn
Affiliations:
University of Calgary, Calgary, AB, Canada
,
C. Silva
Affiliations:
University of Calgary, Calgary, AB, Canada
,
L. Metz
Affiliations:
University of Calgary, Calgary, AB, Canada
V.W. Yong
Affiliations:
University of Calgary, Calgary, AB, Canada
ECTRIMS Learn. Camara C. 10/11/18; 228697; P854
Carlos Camara
Carlos Camara
Contributions
Abstract

Abstract: P854

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Introduction: Patients with Multiple Sclerosis (MS) have increased intestinal permeability. An altered intestinal barrier could lead to the translocation of gut commensals and associated molecules into the circulation that alter immunologic responses.
Objectives and Aims: Our aim was to measure the serum levels of Intestinal Fatty-Acid Binding Protein (IFABP), a marker of intestinal barrier integrity, in patients with early MS/Clinically Isolated Syndrome (CIS). Inflammatory mediators including multiple cytokines, chemokines, growth factors and matrix metalloproteases were also quantified.
Methods: We included Calgary site patients from the Minocycline-CIS trial (Metz et al., New Engl J Med 376:2122, 2017), who experienced a first clinical demyelinating event (29 patients with a mean age of 32.2 ± 9.1 years, where 62% were female). We used 10 age and sex matched healthy individuals as controls and 5 patients with Inflammatory Bowel Disease (IBD) as positive controls (for IFABP levels only). Pre-treatment blood-samples were used to measure IFABP by ELISA and cytokine levels by Luminex® Assay. Clinical (EDSS), demographic and outcome measures (conversion to Definite MS) were analyzed.
Results: Patients with early MS/CIS have higher concentrations of IFABP than controls, indicating an altered intestinal barrier. IFABP levels were not associated with age or sex, but they were significantly correlated with EDSS. When comparing patients with an altered intestinal barrier to those with an intact barrier, we found differences in the concentrations of several immune mediators. Notably, patients with an altered intestinal barrier had higher concentrations of TNF-alpha, MMP-1, and MMP-1/TIMP-1 ratio, while patients with an intact barrier had higher concentrations of GCSF, GMCSF, IP10, MCP-3 and IL-18.
Conclusions: Some patients with early MS/CIS have an altered intestinal barrier. This subgroup also has a distinct immunologic phenotype. The clinical relevance of these differences remains to be elucidated.
Disclosure: Carlos R. Camara-Lemarroy: Nothing to disclose; Jennifer Hahn: Nothing to disclose; Claudia Silva: Nothing to disclose; Luanne Metz: Nothing to disclose; V. Wee Yong: Nothing to disclose

Abstract: P854

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Introduction: Patients with Multiple Sclerosis (MS) have increased intestinal permeability. An altered intestinal barrier could lead to the translocation of gut commensals and associated molecules into the circulation that alter immunologic responses.
Objectives and Aims: Our aim was to measure the serum levels of Intestinal Fatty-Acid Binding Protein (IFABP), a marker of intestinal barrier integrity, in patients with early MS/Clinically Isolated Syndrome (CIS). Inflammatory mediators including multiple cytokines, chemokines, growth factors and matrix metalloproteases were also quantified.
Methods: We included Calgary site patients from the Minocycline-CIS trial (Metz et al., New Engl J Med 376:2122, 2017), who experienced a first clinical demyelinating event (29 patients with a mean age of 32.2 ± 9.1 years, where 62% were female). We used 10 age and sex matched healthy individuals as controls and 5 patients with Inflammatory Bowel Disease (IBD) as positive controls (for IFABP levels only). Pre-treatment blood-samples were used to measure IFABP by ELISA and cytokine levels by Luminex® Assay. Clinical (EDSS), demographic and outcome measures (conversion to Definite MS) were analyzed.
Results: Patients with early MS/CIS have higher concentrations of IFABP than controls, indicating an altered intestinal barrier. IFABP levels were not associated with age or sex, but they were significantly correlated with EDSS. When comparing patients with an altered intestinal barrier to those with an intact barrier, we found differences in the concentrations of several immune mediators. Notably, patients with an altered intestinal barrier had higher concentrations of TNF-alpha, MMP-1, and MMP-1/TIMP-1 ratio, while patients with an intact barrier had higher concentrations of GCSF, GMCSF, IP10, MCP-3 and IL-18.
Conclusions: Some patients with early MS/CIS have an altered intestinal barrier. This subgroup also has a distinct immunologic phenotype. The clinical relevance of these differences remains to be elucidated.
Disclosure: Carlos R. Camara-Lemarroy: Nothing to disclose; Jennifer Hahn: Nothing to disclose; Claudia Silva: Nothing to disclose; Luanne Metz: Nothing to disclose; V. Wee Yong: Nothing to disclose

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