PMID- 34220839
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Short- and Long-Lived Autoantibody-Secreting Cells in Autoimmune Neurological 
      Disorders.
PG  - 686466
LID - 10.3389/fimmu.2021.686466 [doi]
LID - 686466
AB  - As B cells differentiate into antibody-secreting cells (ASCs), short-lived 
      plasmablasts (SLPBs) are produced by a primary extrafollicular response, followed 
      by the generation of memory B cells and long-lived plasma cells (LLPCs) in 
      germinal centers (GCs). Generation of IgG4 antibodies is T helper type 2 (Th2) 
      and IL-4, -13, and -10-driven and can occur parallel to IgE, in response to 
      chronic stimulation by allergens and helminths. Although IgG4 antibodies are 
      non-crosslinking and have limited ability to mobilize complement and cellular 
      cytotoxicity, when self-tolerance is lost, they can disrupt ligand-receptor 
      binding and cause a wide range of autoimmune disorders including neurological 
      autoimmunity. In myasthenia gravis with predominantly IgG4 autoantibodies against 
      muscle-specific kinase (MuSK), it has been observed that one-time CD20(+) B cell 
      depletion with rituximab commonly leads to long-term remission and a marked 
      reduction in autoantibody titer, pointing to a short-lived nature of 
      autoantibody-secreting cells. This is also observed in other predominantly IgG4 
      autoantibody-mediated neurological disorders, such as chronic inflammatory 
      demyelinating polyneuropathy and autoimmune encephalitis with autoantibodies 
      against the Ranvier paranode and juxtaparanode, respectively, and extends beyond 
      neurological autoimmunity as well. Although IgG1 autoantibody-mediated 
      neurological disorders can also respond well to rituximab induction therapy in 
      combination with an autoantibody titer drop, remission tends to be less 
      long-lasting and cases where titers are refractory tend to occur more often than 
      in IgG4 autoimmunity. Moreover, presence of GC-like structures in the thymus of 
      myasthenic patients with predominantly IgG1 autoantibodies against the 
      acetylcholine receptor and in ovarian teratomas of autoimmune encephalitis 
      patients with predominantly IgG1 autoantibodies against the N-methyl-d-aspartate 
      receptor (NMDAR) confers increased the ability to generate LLPCs. Here, we review 
      available information on the short-and long-lived nature of ASCs in IgG1 and IgG4 
      autoantibody-mediated neurological disorders and highlight common mechanisms as 
      well as differences, all of which can inform therapeutic strategies and 
      personalized medical approaches.
CI  - Copyright (c) 2021 Zografou, Vakrakou and Stathopoulos.
FAU - Zografou, C
AU  - Zografou C
AD  - Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
FAU - Vakrakou, A G
AU  - Vakrakou AG
AD  - First Department of Neurology, National and Kapodistrian University of Athens 
      Medical School, Athens, Greece.
FAU - Stathopoulos, P
AU  - Stathopoulos P
AD  - First Department of Neurology, National and Kapodistrian University of Athens 
      Medical School, Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210617
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Cholinergic)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Autoantibodies/*blood
MH  - Autoimmunity
MH  - B-Lymphocytes/immunology
MH  - Humans
MH  - Immunoglobulin G/*blood
MH  - Myasthenia Gravis/drug therapy/*immunology
MH  - Receptor Protein-Tyrosine Kinases/*immunology
MH  - Receptors, Cholinergic/*immunology
MH  - Rituximab/therapeutic use
PMC - PMC8248361
OTO - NOTNLM
OT  - IgG4
OT  - autoantibody-mediated disorders
OT  - long-lived plasma cells
OT  - neurological autoimmunity
OT  - rituximab
OT  - short-lived
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/06 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/01/01
CRDT- 2021/07/05 10:00
PHST- 2021/03/26 00:00 [received]
PHST- 2021/05/28 00:00 [accepted]
PHST- 2021/07/05 10:00 [entrez]
PHST- 2021/07/06 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.686466 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jun 17;12:686466. doi: 10.3389/fimmu.2021.686466. eCollection 
      2021.