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- Title
Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects.
- Authors
Samadzadeh, Sara; Olesen, Mads Nikolaj; Wirenfeldt, Martin; Möller, Sören; Misu, Tatsuro; Soelberg, Kerstin; Frederiksen, Jette Lautrup; Heegaard, Steffen; Mariotto, Sara; Fujihara, Kazuo; Ruprecht, Klemens; Andersen, Thomas Levin; Marignier, Romain; Lillevang, Søren Thue; Flanagan, Eoin P; Pittock, Sean J; Kim, Ho Jin; Bennett, Jeffrey L; Paul, Friedemann; Sorensen, Grith Lykke
- 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.
- Subjects
CENTRAL nervous system diseases; DEMYELINATION; NEUROMYELITIS optica; EXTRACELLULAR matrix proteins; CENTRAL nervous system
- Publication
Multiple Sclerosis Journal, 2023, Vol 29, Issue 14, p1721
- ISSN
1352-4585
- Publication type
Article
- DOI
10.1177/13524585231200720