PMID- 35027475
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20220314
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 9
IP  - 2
DP  - 2022 Mar
TI  - Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated 
      Experimental Autoimmune Encephalomyelitis.
LID - 10.1212/NXI.0000000000001134 [doi]
LID - e1134
AB  - BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein 
      antibody-associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS 
      disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum 
      disorder. Characterized by pathogenic immunoglobulin G (IgG) antibodies against 
      MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG 
      levels, e.g., by interference with the IgG recycling pathway mediated by the 
      neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally 
      involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been 
      assessed. Our objective was to investigate effects of a monoclonal anti-FcRn 
      antibody in murine MOG-IgG-associated experimental autoimmune encephalomyelitis 
      (EAE). METHODS: We induced active MOG(35-55) EAE in C57Bl/6 mice followed by the 
      application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). 
      Animals were treated with either a specific monoclonal antibody against FcRn 
      (alpha-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic 
      disability was scored daily on a 10-point scale. Visual acuity was assessed by 
      optomotor reflex. Histopathologic hallmarks of disease were assessed in the 
      spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by 
      immunohistochemistry, demyelination by Luxol fast blue staining and complement 
      deposition and number of retinal ganglion cells by immunofluorescence. RESULTS: 
      In MOG-IgG-augmented MOG(35-55) EAE, anti-FcRn treatment significantly attenuated 
      neurologic disability over the course of disease (mean area under the curve and 
      95% confidence intervals (CIs): alpha-FcRn [n = 27], 46.02 [37.89-54.15]; isotype IgG 
      [n = 24], 66.75 [59.54-73.96], 3 independent experiments), correlating with 
      reduced amounts of demyelination and macrophage infiltration into the spinal 
      cord. T- and B-cell infiltration and complement deposition remained unchanged. 
      Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity 
      over the course of disease (median cycles/degree and interquartile range: alpha-FcRn 
      [n = 16], 0.50 [0.48-0.55] to 0.50 [0.48-0.58]; isotype IgG [n = 17], 0.50 
      [0.49-0.54] to 0.45 [0.39-0.51]). DISCUSSION: We show preserved optomotor 
      response and ameliorated course of disease after anti-FcRn treatment in an 
      experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively 
      targeting FcRn might represent a promising therapeutic approach in MOGAD.
CI  - Copyright (c) 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Remlinger, Jana
AU  - Remlinger J
AUID- ORCID: 0000-0002-6502-4383
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Madarasz, Adrian
AU  - Madarasz A
AUID- ORCID: 0000-0002-9411-0272
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Guse, Kirsten
AU  - Guse K
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Hoepner, Robert
AU  - Hoepner R
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Bagnoud, Maud
AU  - Bagnoud M
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Meli, Ivo
AU  - Meli I
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Feil, Moritz
AU  - Feil M
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Abegg, Mathias
AU  - Abegg M
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Linington, Christopher
AU  - Linington C
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Shock, Anthony
AU  - Shock A
AUID- ORCID: 0000-0002-9971-8789
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Boroojerdi, Babak
AU  - Boroojerdi B
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Kiessling, Peter
AU  - Kiessling P
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Smith, Bryan
AU  - Smith B
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Enzmann, Volker
AU  - Enzmann V
AUID- ORCID: 0000-0003-4384-4855
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Chan, Andrew
AU  - Chan A
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany.
FAU - Salmen, Anke
AU  - Salmen A
AUID- ORCID: 0000-0002-4751-299X
AD  - From the Department of Neurology (J.R., A.M., K.G., R.H., M.B., I.M., A.C., A. 
      Salmen), Inselspital, Bern University Hospital and University of Bern; Department 
      of Biomedical Research (J.R., A.M., K.G., R.H., M.B., I.M., V.E., A.C., A. 
      Salmen), and Graduate School for Cellular and Biomedical Sciences (J.R., A.M., 
      M.B.), University of Bern; Department of Ophthalmology (M.F., M.A., V.E.), 
      Inselspital, Bern University Hospital and University of Bern, Switzerland; 
      Institute of Infection (C.L.), Immunity and Inflammation, University of Glasgow; 
      UCB Pharma (A. Shock, B.S.), Slough, United Kingdom; and UCB Pharma (B.B., P.K.), 
      Monheim-am-Rhein, Germany. anke.salmen@insel.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220113
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Receptors, Fc)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Encephalomyelitis, Autoimmune, Experimental/complications/*drug 
      therapy/etiology/*immunology
MH  - Female
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin-Oligodendrocyte Glycoprotein/*immunology
MH  - Receptors, Fc/*immunology
MH  - Vision Disorders
PMC - PMC8759074
EDAT- 2022/01/15 06:00
MHDA- 2022/03/15 06:00
PMCR- 2022/01/13
CRDT- 2022/01/14 05:44
PHST- 2021/08/19 00:00 [received]
PHST- 2021/12/03 00:00 [accepted]
PHST- 2022/01/14 05:44 [entrez]
PHST- 2022/01/15 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2022/01/13 00:00 [pmc-release]
AID - 9/2/e1134 [pii]
AID - NEURIMMINFL2021039382 [pii]
AID - 10.1212/NXI.0000000000001134 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2022 Jan 13;9(2):e1134. doi: 
      10.1212/NXI.0000000000001134. Print 2022 Mar.