Citations 2
Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects
Samadzadeh, Sara , Olesen, Mads Nikolaj , Wirenfeldt, Martin , Möller, Sören , Misu, Tatsuro , Soelberg, Kerstin , Frederiksen, Jette Lautrup , Ruprecht, Klemens , Andersen, Thomas Levin , Marignier, Romain , Lillevang, Søren Thue , Pittock, Sean J, Kim, Ho Jin , Bennett, Jeffrey L. , Paul, Friedemann , Sørensen, Grith Lykke , Weinshenker, Brian G. , Pittock, Sean J. , Pittock, S J , Marignier, Romain , Flanagan, E P , Pittock, Sean J , Kim, Ho Jin , Bennett, Jeffrey L , Weinshenker, Brian G , Paul, Friedemann , Heegaard, Steffen , Mariotto, Sara , Fujihara, Kazuo , Flanagan, Eoin P. , Lassmann, Hans , Asgari, Nasrin
Multiple Sclerosis Journal | October 13, 2023 | Volume: 29 | Issue: 14 | Pages: 1721-1735
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.
Microfibrillar-associated Protein 4 as Potential Marker of Acute Relapse in Inflammatory Demyelinating Diseases of the Central Nervous System: Pathological and Clinical Aspects
Olesen, Mads Nikolaj , Wirenfeldt, Martin , Ruprecht, Klemens , Marignier, Romain , Lillevang, Søren Thue , Pittock, Sean J. , Kim, Ho Jin , Pittock, S J , Samadzadeh, Sara , Möller, Sören , Misu, Tatsuro , Soelberg, Kerstin , Frederiksen, Jette Lautrup , Heegaard, Steffen , Mariotto, Sara , Fujihara, Kazuo , Andersen, Thomas Levin , Flanagan, Eoin P. , Bennett, Jeffrey L. , Paul, Friedemann , Sørensen, Grith Lykke , Weinshenker, Brian G. , Lassmann, Hans , Asgari, Nasrin
No container title available | April 12, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
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.