Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis

Madhurima Chatterjee, Marleen Ja Koel-Simmelink, Inge Mw Verberk, Joep Killestein, Hugo Vrenken, Christian Enzinger, Stefan Ropele, Franz Fazekas, Michael Khalil, Charlotte E Teunissen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity.

Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration.

Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing-remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features.

Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing-remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = -0.42, p = 0.04) predicted the longitudinal decline in cortex volume.

Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.

Original languageEnglish
Pages (from-to)2055217318819535
JournalMultiple sclerosis journal - experimental, translational and clinical
Volume4
Issue number4
DOIs
Publication statusPublished - 11 Jan 2019

Cite this

@article{2e275d836be74954ba8d0cd02ba341bc,
title = "Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis",
abstract = "Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity.Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration.Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing-remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features.Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing-remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = -0.42, p = 0.04) predicted the longitudinal decline in cortex volume.Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.",
author = "Madhurima Chatterjee and Koel-Simmelink, {Marleen Ja} and Verberk, {Inge Mw} and Joep Killestein and Hugo Vrenken and Christian Enzinger and Stefan Ropele and Franz Fazekas and Michael Khalil and Teunissen, {Charlotte E}",
year = "2019",
month = "1",
day = "11",
doi = "10.1177/2055217318819535",
language = "English",
volume = "4",
pages = "2055217318819535",
journal = "Multiple sclerosis journal - experimental, translational and clinical",
issn = "2055-2173",
number = "4",

}

TY - JOUR

T1 - Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis

AU - Chatterjee, Madhurima

AU - Koel-Simmelink, Marleen Ja

AU - Verberk, Inge Mw

AU - Killestein, Joep

AU - Vrenken, Hugo

AU - Enzinger, Christian

AU - Ropele, Stefan

AU - Fazekas, Franz

AU - Khalil, Michael

AU - Teunissen, Charlotte E

PY - 2019/1/11

Y1 - 2019/1/11

N2 - Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity.Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration.Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing-remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features.Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing-remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = -0.42, p = 0.04) predicted the longitudinal decline in cortex volume.Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.

AB - Background: Contactin-1 and contactin-2 are important for the maintenance of axonal integrity.Objective: To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration.Methods: Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing-remitting multiple sclerosis (n = 41), secondary progressive multiple sclerosis (n = 26) and primary progressive multiple sclerosis patients (n = 13) and controls (n = 18), and in a second cohort with clinically isolated syndrome patients (n = 88, median clinical follow-up period of 2.3 years) and controls (n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features.Results: Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing-remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls (p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = -0.42, p = 0.04) predicted the longitudinal decline in cortex volume.Conclusion: Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.

U2 - 10.1177/2055217318819535

DO - 10.1177/2055217318819535

M3 - Article

VL - 4

SP - 2055217318819535

JO - Multiple sclerosis journal - experimental, translational and clinical

JF - Multiple sclerosis journal - experimental, translational and clinical

SN - 2055-2173

IS - 4

ER -