Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects

Sara Samadzadeh, Mads Nikolaj Olesen, Martin Wirenfeldt, Sören Möller, Tatsuro Misu, Kerstin Soelberg, Jette Lautrup Frederiksen, Steffen Heegaard, Sara Mariotto, Kazuo Fujihara, Klemens Ruprecht, Thomas Levin Andersen, Romain Marignier, Søren Thue Lillevang, Eoin P Flanagan, Sean J Pittock, Ho Jin Kim, Jeffrey L Bennett, Friedemann Paul, Grith Lykke SorensenBrian G Weinshenker, Hans Lassmann, Nasrin Asgari*

*Corresponding author af dette arbejde

Abstract

BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein not previously described in the human central nervous system (CNS).

OBJECTIVES: We determined MFAP4 CNS expression and measured cerebrospinal fluid (CSF) and serum levels.

METHODS: Tissue was sampled at autopsy from patients with acute multiple sclerosis (MS) (n = 3), progressive MS (n = 3), neuromyelitis optica spectrum disorder (NMOSD) (n = 2), and controls (n = 9), including 6 healthy controls (HC). MFAP4 levels were measured in 152 patients: 49 MS, 62 NMOSD, 22 myelin oligodendrocyte glycoprotein-associated disease (MOGAD), and 19 isolated optic neuritis (ION).

RESULTS: MFAP4 localized to meninges and vascular/perivascular spaces, intense in the optic nerve. At sites of active inflammation, MFAP4 reactivity was reduced in NMOSD and acute MS and less in progressive MS. CSF MFAP4 levels were reduced during relapse and at the onset of diseases (mean U/mL: MS 14.3, MOGAD 9.7, and ION 14.6 relative to HC 17.9. (p = 0.013, p = 0.000, and p = 0.019, respectively). Patients with acute ON (n = 68) had reduced CSF MFAP4 (mean U/mL: 14.5, p = 0.006). CSF MFAP4 levels correlated negatively with relapse severity (rho = -0.41, p = 0.017).

CONCLUSION: MFAP4 immunoreactivity was reduced at sites of active inflammation. CSF levels of MFAP4 were reduced following relapse and may reflect disease activity.

OriginalsprogEngelsk
TidsskriftMultiple Sclerosis Journal
Vol/bind29
Udgave nummer14
Sider (fra-til)1721-1735
Antal sider15
ISSN1352-4585
DOI
StatusUdgivet - dec. 2023

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