Citations

Abstract Background and Objectives: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein not previously described in the central nervous system (CNS). We aimed to determine MFAP4 CNS expression and measure 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), 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 the meninges and the vascular/perivascular spaces, particularly intense in the optic nerve. At sites of active inflammation, MFAP4 reactivity was reduced in NMOSD and acute MS and to a lesser degree in progressive MS. CSF MFAP4 levels were reduced in patients during acute attacks compared to HC. There was a positive correlation between number of relapses and CSF MFAP4 levels (rho=0.33, p=0.004). CSF MFAP4 levels were lower in 53 samples obtained at presenting attack (mean U/mL: 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). All patients with acute ON relapse (n=68) had reduced CSF MFAP4 relative to HC (mean U/mL: 14.5 vs. 17.9, p=0.006). CSF MFAP4 levels correlated negatively with relapse severity (rho=-0.41, p=0.017). Discussion.: MFAP4 immunoreactivity was observed in CNS and reduced at sites of active inflammation. CSF levels of MFAP4 were reduced following acute relapse and may serve as a marker of disease activity and attack severity.