TY - JOUR

T1 - Biomarkers of inflammation and epithelial barrier function in multiple sclerosis

AU - Olsson, A.

AU - Gustavsen, S.

AU - Hasselbalch, I. Chenoufi

AU - Langkilde, A. R.

AU - Sellebjerg, F.

AU - Oturai, A. B.

AU - Søndergaard, H. Bach

PY - 2020

Y1 - 2020

N2 - Background: There is a lack of reliable biomarkers predicting disability and disease activity in multiple sclerosis (MS). Recent evidence suggests an involvement of intestinal and pulmonary epithelial barrier function related to immune activation and the pathophysiology of MS. Blood biomarkers of epithelial barrier function have, however, not been widely studied in MS. Objective: To examine biomarkers of inflammation and epithelial barrier function in relapsing remitting MS (RRMS) patients compared with healthy controls (HCs), and to assess associations between biomarkers and disease activity. Methods: A panel of 30 biomarkers were measured in serum or plasma from 49 newly diagnosed, untreated RRMS patients and 58 HCs with electrochemiluminescence or ELISA. Neurofilament light chain (NfL) was measured with single-molecule array. Validation was performed in a second independent cohort of 68 newly diagnosed, treatment naive RRMS patients and 50 HCs. Patients were divided into groups of active and inactive disease based on NfL levels and the presence of gadolinium enhancing magnetic resonance imaging lesions. Results: Patients with active MS showed significantly higher serum levels of calprotectin and soluble urokinase plasminogen activator receptor compared with inactive MS in the exploratory cohort. Validation confirmed higher levels of calprotectin in active compared with inactive MS, and HCs. Biomarkers of intestinal and pulmonary epithelial barrier function did not differ significantly between groups. Conclusions: The measured biomarkers of epithelial barrier function do not seem to play a major role in the pathophysiology of MS, but serum calprotectin could represent a clinically useful biomarker of innate immune activation and disease activity.

AB - Background: There is a lack of reliable biomarkers predicting disability and disease activity in multiple sclerosis (MS). Recent evidence suggests an involvement of intestinal and pulmonary epithelial barrier function related to immune activation and the pathophysiology of MS. Blood biomarkers of epithelial barrier function have, however, not been widely studied in MS. Objective: To examine biomarkers of inflammation and epithelial barrier function in relapsing remitting MS (RRMS) patients compared with healthy controls (HCs), and to assess associations between biomarkers and disease activity. Methods: A panel of 30 biomarkers were measured in serum or plasma from 49 newly diagnosed, untreated RRMS patients and 58 HCs with electrochemiluminescence or ELISA. Neurofilament light chain (NfL) was measured with single-molecule array. Validation was performed in a second independent cohort of 68 newly diagnosed, treatment naive RRMS patients and 50 HCs. Patients were divided into groups of active and inactive disease based on NfL levels and the presence of gadolinium enhancing magnetic resonance imaging lesions. Results: Patients with active MS showed significantly higher serum levels of calprotectin and soluble urokinase plasminogen activator receptor compared with inactive MS in the exploratory cohort. Validation confirmed higher levels of calprotectin in active compared with inactive MS, and HCs. Biomarkers of intestinal and pulmonary epithelial barrier function did not differ significantly between groups. Conclusions: The measured biomarkers of epithelial barrier function do not seem to play a major role in the pathophysiology of MS, but serum calprotectin could represent a clinically useful biomarker of innate immune activation and disease activity.

KW - Biomarkers

KW - Calprotectin

KW - Intestinal permeability

KW - Neurofilament light chain

KW - Zonulin

U2 - 10.1016/j.msard.2020.102520

DO - 10.1016/j.msard.2020.102520

M3 - Journal article

C2 - 32980645

AN - SCOPUS:85091481409

VL - 46

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

M1 - 102520

ER -