Autoimmune mechanisms in myasthenia gravis

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Purpose of Review: This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process. Recent Findings: Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients. Summary: The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalCurrent Opinion in Neurology
Volume25
Issue number5
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Myasthenia Gravis
Autoimmunity
Autoantibodies
LDL-Receptor Related Proteins
Lipoprotein Receptors
LDL Receptors
Autoantigens
Virus Diseases
Regulatory T-Lymphocytes
Thymus Gland
Phosphotransferases
Maintenance
Inflammation
Antibodies
Therapeutics

Keywords

  • autoantibodies
  • autoimmunity
  • myasthenia gravis
  • thymus

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Autoimmune mechanisms in myasthenia gravis. / Cavalcante, Paola; Bernasconi, Pia; Mantegazza, Renato.

In: Current Opinion in Neurology, Vol. 25, No. 5, 10.2012, p. 621-629.

Research output: Contribution to journalArticle

@article{07c26afa5faf4cd4a25bf2543dbdd8ab,
title = "Autoimmune mechanisms in myasthenia gravis",
abstract = "Purpose of Review: This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process. Recent Findings: Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients. Summary: The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.",
keywords = "autoantibodies, autoimmunity, myasthenia gravis, thymus",
author = "Paola Cavalcante and Pia Bernasconi and Renato Mantegazza",
year = "2012",
month = "10",
doi = "10.1097/WCO.0b013e328357a829",
language = "English",
volume = "25",
pages = "621--629",
journal = "Current Opinion in Neurology",
issn = "1350-7540",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Autoimmune mechanisms in myasthenia gravis

AU - Cavalcante, Paola

AU - Bernasconi, Pia

AU - Mantegazza, Renato

PY - 2012/10

Y1 - 2012/10

N2 - Purpose of Review: This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process. Recent Findings: Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients. Summary: The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.

AB - Purpose of Review: This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process. Recent Findings: Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients. Summary: The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.

KW - autoantibodies

KW - autoimmunity

KW - myasthenia gravis

KW - thymus

UR - http://www.scopus.com/inward/record.url?scp=84866334495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866334495&partnerID=8YFLogxK

U2 - 10.1097/WCO.0b013e328357a829

DO - 10.1097/WCO.0b013e328357a829

M3 - Article

VL - 25

SP - 621

EP - 629

JO - Current Opinion in Neurology

JF - Current Opinion in Neurology

SN - 1350-7540

IS - 5

ER -