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 - 24 Dec 2018

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