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

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Item Type:	Article
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
Creators Name:	Samadzadeh, S., Olesen, M.N., Wirenfeldt, M., Möller, S., Misu, T., Soelberg, K., Frederiksen, J.L., Heegaard, S., Mariotto, S., Fujihara, K., Ruprecht, K., Andersen, T.L., Marignier, R., Lillevang, S.T., Flanagan, E.P., Pittock, S.J., Kim, H.J., Bennett, J.L., Paul, F., Sorensen, G.L., Weinshenker, B.G., Lassmann, H. and Asgari, N.
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.
Keywords:	Inflammatory Demyelinating Diseases, Central Nervous System, Microfibrillar-Associated Protein 4, Relapse
Source:	Multiple Sclerosis Journal
ISSN:	1352-4585
Publisher:	Sage Publications
Volume:	29
Number:	14
Page Range:	1721-1735
Date:	14 December 2023
Official Publication:	https://doi.org/10.1177/13524585231200720
PubMed:	View item in PubMed

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