PMID- 32117321
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20210308
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Autoantibody Specificities in Myasthenia Gravis; Implications for Improved 
      Diagnostics and Therapeutics.
PG  - 212
LID - 10.3389/fimmu.2020.00212 [doi]
LID - 212
AB  - Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness 
      and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused 
      by autoantibodies targeting neuromuscular junction proteins. In the majority of 
      patients (~85%) antibodies against the muscle acetylcholine receptor (AChR) are 
      detected, while in 6% antibodies against the muscle-specific kinase (MuSK) are 
      detected. In ~10% of MG patients no autoantibodies can be found with the 
      classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG), 
      making the improvement of methods for the detection of known autoantibodies or 
      the discovery of novel antigenic targets imperative. Over the past years, using 
      cell-based assays or improved highly sensitive immunoprecipitation assays, it has 
      been possible to detect autoantibodies in previously SN-MG patients, including 
      the identification of the low-density lipoprotein receptor-related protein 4 
      (LRP4) as a third MG autoantigen, as well as AChR and MuSK antibodies 
      undetectable by conventional methods. Furthermore, antibodies against other 
      extracellular or intracellular targets, such as titin, the ryanodine receptor, 
      agrin, collagen Q, K(v)1.4 potassium channels and cortactin have been found in 
      some MG patients, which can be useful biomarkers. In addition to the improvement 
      of diagnosis, the identification of the patients' autoantibody specificity is 
      important for their stratification into respective subgroups, which can differ in 
      terms of clinical manifestations, prognosis and most importantly their response 
      to therapies. The knowledge of the autoantibody profile of MG patients would 
      allow for a therapeutic strategy tailored to their MG subgroup. This is becoming 
      especially relevant as there is increasing progress toward the development of 
      antigen-specific therapies, targeting only the specific autoantibodies or immune 
      cells involved in the autoimmune response, such as antigen-specific 
      immunoadsorption, which have shown promising results. We will herein review the 
      advances made by us and others toward development of more sensitive detection 
      methods and the identification of new antibody targets in MG, and discuss their 
      significance in MG diagnosis and therapy. Overall, the development of novel 
      autoantibody assays is aiding in the more accurate diagnosis and classification 
      of MG patients, supporting the development of advanced therapeutics and 
      ultimately the improvement of disease management and patient quality of life.
CI  - Copyright (c) 2020 Lazaridis and Tzartos.
FAU - Lazaridis, Konstantinos
AU  - Lazaridis K
AD  - Department of Immunology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Tzartos, Socrates J
AU  - Tzartos SJ
AD  - Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
AD  - Tzartos NeuroDiagnostics, Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200214
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Autoantibodies)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - *Antibody Specificity
MH  - Autoantibodies/*blood/immunology
MH  - Humans
MH  - Myasthenia Gravis/diagnosis/*immunology/therapy
MH  - Receptor Protein-Tyrosine Kinases/immunology
MH  - Receptors, Cholinergic/immunology
MH  - Ryanodine Receptor Calcium Release Channel/immunology
PMC - PMC7033452
OTO - NOTNLM
OT  - LRP4
OT  - MuSK
OT  - acetylcholine receptor
OT  - autoantibody
OT  - autoimmunity
OT  - diagnosis
OT  - myasthenia gravis
OT  - therapy
EDAT- 2020/03/03 06:00
MHDA- 2021/03/09 06:00
PMCR- 2020/01/01
CRDT- 2020/03/03 06:00
PHST- 2019/11/09 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/03/03 06:00 [entrez]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.00212 [doi]
PST - epublish
SO  - Front Immunol. 2020 Feb 14;11:212. doi: 10.3389/fimmu.2020.00212. eCollection 
      2020.