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Lookup NU author(s): Professor Jordi Diaz ManeraORCiD
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© 2014 Elsevier B.V. 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.
Author(s): Gallardo E, Martinez-Hernandez E, Titulaer MJ, Huijbers MG, Martinez MA, Ramos A, Querol L, Diaz-Manera J, Rojas-Garcia R, Hayworth CR, Verschuuren JJ, Balice-Gordon R, Dalmau J, Illa I
Publication type: Review
Publication status: Published
Journal: Autoimmunity Reviews
Print publication date: 01/10/2014
Online publication date: 03/09/2014
Acceptance date: 25/06/2014
ISSN (print): 1568-9972
ISSN (electronic): 1873-0183
PubMed id: 25193850