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

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) (

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. (

CONCLUSION

MFAP4 immunoreactivity was reduced at sites of active inflammation. CSF levels of MFAP4 were reduced following relapse and may reflect disease activity.

Déclaration de conflit d'intérêts

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.S., M.N.O., M.W., S.M., S.T.L., K.S., and N.A. have nothing to disclose.T.M. has received speaker honoraria from Tanabe Mitsubishi Pharma, Novartis Pharma., Alexion Pharma., Teijin Pharma., Viela Bio, and Biogen Idec Japan; he has received research support from Cosmic Corporation, and Medical and Biological Laboratories Co.; and grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology.J.F. has served on scientific advisory boards for and received funding for travel related to these activities as well as honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis, and Almirall.S.H. is a scientific advisor for Alcon, Santen, Sanofi, and Thea.S.MA. has received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen.K.F. has received grants from the Ministry of Education of Japan, Ministry of Health, Welfare and Labor of Japan, and received personal fees from Roche/Chugai, Alexion, Viela Bio/ Horizon Therapeutics, Biogen, Eisai, Mitsubishi Tanabe, Novartis, Astellas, Tejin, Takeda, UCB, Merck Biopharma, Abbvie, Japan Tobacco, and Asahi Kasei Medical.K.R. has received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821283-2), Stiftung Charité (BIH Clinical Fellow Program), and Arthur Arnstein Foundation; and received travel grants from the Guthy-Jackson Charitable Foundation.T.L.A. has received nonfinancial support from Amgen, and free reagents from 10X genomics and ABD bioscience for projects outside the submitted work.R.M. reports personal fees from Alexion, Horizon Therapeutics, Merck, Biogen, Roche, and UCB, outside the submitted work.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.S.P. has received personal compensation for serving as a consultant for Genentech, Sage Therapeutics, and Astellas. He has received personal compensation for serving on scientific advisory boards or data safety monitoring boards for F. Hoffman-LaRoche AG, Genentech, and UCB. His institution has received compensation for serving as a consultant for Astellas, Alexion, and Viela Bio/MedImmune. All compensation is paid to Mayo Clinic. He has received research support from Alexion, Viela Bio/MedImmune, Roche/Genentech. He has a patent, Patent# 8,889,102 (Application#12-678350, Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia)—issued; a patent, Patent# 9,891,219B2 (Application#12-573942, Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive)—issued.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