PMID- 32547535
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20240328
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by 
      Divergent Mechanisms of Immunopathology.
PG  - 776
LID - 10.3389/fimmu.2020.00776 [doi]
LID - 776
AB  - Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The 
      autoantibodies in MG target structures within the neuromuscular junction (NMJ), 
      thus affecting neuromuscular transmission. The major disease subtypes of 
      autoimmune MG are defined by their antigenic target. The most common target of 
      pathogenic autoantibodies in MG is the nicotinic acetylcholine receptor (AChR), 
      followed by muscle-specific kinase (MuSK) and lipoprotein receptor-related 
      protein 4 (LRP4). MG patients present with similar symptoms independent of the 
      underlying subtype of disease, while the immunopathology is remarkably distinct. 
      Here we highlight these distinct immune mechanisms that describe both the B cell- 
      and autoantibody-mediated pathogenesis by comparing AChR and MuSK MG subtypes. In 
      our discussion of the AChR subtype, we focus on the role of long-lived plasma 
      cells in the production of pathogenic autoantibodies, the IgG1 subclass mediated 
      pathology, and contributions of complement. The similarities underlying the 
      immunopathology of AChR MG and neuromyelitis optica (NMO) are highlighted. In 
      contrast, MuSK MG is caused by autoantibody production by short-lived 
      plasmablasts. MuSK MG autoantibodies are mainly of the IgG4 subclass which can 
      undergo Fab-arm exchange (FAE), a process unique to this subclass. In FAE IgG4, 
      molecules can dissociate into two halves and recombine with other half IgG4 
      molecules resulting in bispecific antibodies. Similarities between MuSK MG and 
      other IgG4-mediated autoimmune diseases, including pemphigus vulgaris (PV) and 
      chronic inflammatory demyelinating polyneuropathy (CIDP), are highlighted. 
      Finally, the immunological distinctions are emphasized through presentation of 
      biological therapeutics that provide clinical benefit depending on the MG disease 
      subtype.
CI  - Copyright (c) 2020 Fichtner, Jiang, Bourke, Nowak and O'Connor.
FAU - Fichtner, Miriam L
AU  - Fichtner ML
AD  - Department of Neurology, School of Medicine, Yale University, New Haven, CT, 
      United States.
AD  - Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, 
      United States.
FAU - Jiang, Ruoyi
AU  - Jiang R
AD  - Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, 
      United States.
FAU - Bourke, Aoibh
AU  - Bourke A
AD  - Trinity Hall, University of Cambridge, Cambridge, United Kingdom.
FAU - Nowak, Richard J
AU  - Nowak RJ
AD  - Department of Neurology, School of Medicine, Yale University, New Haven, CT, 
      United States.
FAU - O'Connor, Kevin C
AU  - O'Connor KC
AD  - Department of Neurology, School of Medicine, Yale University, New Haven, CT, 
      United States.
AD  - Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, 
      United States.
LA  - eng
GR  - R01 AI114780/AI/NIAID NIH HHS/United States
GR  - R21 AI142198/AI/NIAID NIH HHS/United States
GR  - T32 GM007205/GM/NIGMS NIH HHS/United States
GR  - U54 NS115054/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200527
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Autoantibodies)
RN  - 0 (CHRNG protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (LRP4 protein, human)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Receptors, Nicotinic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Bispecific
MH  - Autoantibodies/*immunology
MH  - B-Lymphocytes/metabolism
MH  - Humans
MH  - Immunoglobulin G
MH  - LDL-Receptor Related Proteins
MH  - Mice
MH  - Myasthenia Gravis/*immunology/*physiopathology/therapy
MH  - Pemphigus
MH  - Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
MH  - Receptor Protein-Tyrosine Kinases
MH  - Receptors, Cholinergic/immunology/metabolism
MH  - Receptors, Nicotinic
PMC - PMC7274207
OTO - NOTNLM
OT  - MuSK
OT  - AChR
OT  - B cells
OT  - B lymphocytes
OT  - autoantibodies
OT  - autoimmunity
OT  - immunopathology
OT  - myasthenia gravis
EDAT- 2020/06/18 06:00
MHDA- 2021/03/23 06:00
PMCR- 2020/01/01
CRDT- 2020/06/18 06:00
PHST- 2020/01/13 00:00 [received]
PHST- 2020/04/06 00:00 [accepted]
PHST- 2020/06/18 06:00 [entrez]
PHST- 2020/06/18 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.00776 [doi]
PST - epublish
SO  - Front Immunol. 2020 May 27;11:776. doi: 10.3389/fimmu.2020.00776. eCollection 
      2020.