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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Multiple Sclerosis Journal |
| Vol/bind | 29 |
| Udgave nummer | 14 |
| Sider (fra-til) | 1721-1735 |
| ISSN | 1352-4585 |
| DOI | |
| Status | Udgivet - dec. 2023 |
Bibliografisk note
Funding Information:J.B. reports personal fees from Roche, Genentech, Horizon, Chugai Pharma, Clene Nanoscience, Reistone-Bio, Beigene, grants and personal fees from Alexion, grants from National Institutes of Health, and has a patent Aquaporumab issued.
Funding Information:
E.F. has served on advisory boards for Alexion, Genentech, and Horizon Therapeutics. He has received speaker honoraria from Pharmacy Times, and royalties from UpToDate. He was a site primary investigator in a randomized clinical trial on Inebilizumab in neuromyelitis optica spectrum disorder run by Medimmune/Viela-Bio/Horizon Therapeutics. He has received funding from the NIH (R01NS113828), is a member of the medical advisory board of the MOG project, and an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports.
Funding Information:
H.J.K. received a grant from the National Research Foundation of Korea and research support from Aprilbio and Eisai; received consultancy/speaker fees from Alexion, Aprilbio, Altos Biologics, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, HanAll BioPharma, Handok, Horizon Therapeutics (formerly Viela Bio), MDimune, Mitsubishi Tanabe Pharma, Merck Serono, Novartis, Roche, Sanofi, Teva-Handok, and UCB; is a co-editor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research was supported by the Danish Multiple Sclerosis Society (A40208, A38376, A35152), The University of Southern Denmark, and the Slagelse Hospital Research Fund.