PMID- 24389034
OWN - NLM
STAT- MEDLINE
DCOM- 20150416
LR  - 20220330
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Linking)
VI  - 52
DP  - 2014 Aug
TI  - Myasthenia gravis: a comprehensive review of immune dysregulation and etiological 
      mechanisms.
PG  - 90-100
LID - S0896-8411(13)00158-3 [pii]
LID - 10.1016/j.jaut.2013.12.011 [doi]
AB  - Autoimmune myasthenia gravis (MG) is characterized by muscle weakness caused by 
      antibodies directed against proteins of the neuromuscular junction. The main 
      antigenic target is the acetylcholine receptor (AChR), but the muscle Specific 
      Kinase (MuSK) and the low-density lipoprotein receptor-related protein (LRP4) are 
      also targets. This review summarizes the clinical and biological data available 
      for different subgroups of patients, who are classified according to antigenic 
      target, age of onset, and observed thymic abnormalities, such as follicular 
      hyperplasia or thymoma. Here, we analyze in detail the role of the thymus in the 
      physiopathology of MG and propose an explanation for the development of the 
      thymic follicular hyperplasia that is commonly observed in young female patients 
      with anti-AChR antibodies. The influence of the pro-inflammatory environment is 
      discussed, particularly the role of TNF-alpha and Th17-related cytokines, which could 
      explain the escape of thymic T cells from regulation and the chronic inflammation 
      in the MG thymus. Together with this immune dysregulation, active angiogenic 
      processes and the upregulation of chemokines could promote thymic follicular 
      hyperplasia. MG is a multifactorial disease, and we review the etiological 
      mechanisms that could lead to its onset. Recent global genetic analyses have 
      highlighted potential susceptibility genes. In addition, miRNAs, which play a 
      crucial role in immune function, have been implicated in MG by recent studies. We 
      also discuss the role of sex hormones and the influence of environmental factors, 
      such as the viral hypothesis. This hypothesis is supported by reports that type I 
      interferon and molecules mimicking viral infection can induce thymic changes 
      similar to those observed in MG patients with anti-AChR antibodies.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Berrih-Aknin, Sonia
AU  - Berrih-Aknin S
AD  - INSERM U974, Paris, France; CNRS UMR 7215, Paris, France; UPMC Univ Paris 6, 
      Paris, France; AIM, Institute of myology, Paris, France. Electronic address: 
      sonia.berrih-aknin@upmc.fr.
FAU - Le Panse, Rozen
AU  - Le Panse R
AD  - INSERM U974, Paris, France; CNRS UMR 7215, Paris, France; UPMC Univ Paris 6, 
      Paris, France; AIM, Institute of myology, Paris, France. Electronic address: 
      rozen.lepanse@upmc.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140103
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Autoantibodies)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Autoantibodies/metabolism
MH  - Humans
MH  - Hyperplasia
MH  - Lipoproteins, LDL/immunology
MH  - MicroRNAs/genetics/metabolism
MH  - Myasthenia Gravis/etiology/*immunology
MH  - Receptor Protein-Tyrosine Kinases/immunology
MH  - Receptors, Cholinergic/immunology
MH  - Th1 Cells/immunology
MH  - Th17 Cells/immunology
MH  - Thymoma/etiology/*immunology
MH  - Thymus Gland/*pathology
MH  - Thymus Neoplasms/etiology/*immunology
MH  - Virus Diseases/complications/*immunology
OTO - NOTNLM
OT  - Genetics
OT  - Germinal centers
OT  - IL-17
OT  - Inflammation
OT  - Treg cells
OT  - miRNA
EDAT- 2014/01/07 06:00
MHDA- 2015/04/17 06:00
CRDT- 2014/01/07 06:00
PHST- 2013/07/29 00:00 [received]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2015/04/17 06:00 [medline]
AID - S0896-8411(13)00158-3 [pii]
AID - 10.1016/j.jaut.2013.12.011 [doi]
PST - ppublish
SO  - J Autoimmun. 2014 Aug;52:90-100. doi: 10.1016/j.jaut.2013.12.011. Epub 2014 Jan 
      3.