Cortactin autoantibodies in myasthenia gravis.

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness, fatigability, and autoantibodies against protein antigens of the muscle endplate. Antibodies against acetylcholine receptor (AChR), and less frequently against muscle-Specific Kinase (MuSK) or lipoprotein related protein 4 (LRP4) occur in patients with seropositive MG (SPMG). However, about 10% of patients do not have detectable autoantibodies despite evidence suggesting that the disorder is immune mediated; this disorder is known as seronegative MG (SNMG). Using a protein array approach we identified cortactin (a protein that acts downstream from agrin/MuSK promoting AChR clustering) as potential new target antigen in SNMG. We set up an ELISA assay and screened sera from patients with SPMG, SNMG, other autoimmune diseases and controls. Results were validated by immunoblot. We found that 19.7% of patients with SNMG had antibodies against cortactin whereas only 4.8% of patients with SPMG were positive. Cortactin antibodies were also found in 12.5% of patients with other autoimmune disorders but only in 5.2% of healthy controls. We conclude that the finding of cortactin antibodies in patients with SNMG, suggests an underlying autoimmune mechanism, supporting the use of immune therapy.

• Authors: Eduard Gallardo, Eugenia Martínez-Hernández, Maarten J Titulaer, Maartje G Huijbers, Maria Angeles Martínez, Alba Ramos, Luis Querol, Jordi Díaz-Manera, Ricard Rojas-García, Christopher R Hayworth, Jan J Verschuuren, Rita Balice-Gordon, Josep Dalmau, Isabel Illa
• Journal: Autoimmunity reviews (Autoimmun Rev) Vol. 13 Issue 10 Pg. 1003-7 (Oct 2014) ISSN: 1873-0183 [Electronic] Netherlands
• PMID: 25193850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Autoantibodies
• CTTN protein, human
• Cortactin
• Receptors, Cholinergic

Topics

• Autoantibodies (analysis, immunology)
• Cortactin (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Myasthenia Gravis (immunology)
• Protein Array Analysis
• Receptors, Cholinergic (immunology)