title: 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.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martínez-Hernández
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Huijbers
authors.affiliation: Department of Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Martínez
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Ramos
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Querol
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Díaz-Manera
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-García
authors.affiliation: Department of Neuroscience, University of Pennsylvania, PA, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Hayworth
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Verschuuren
authors.affiliation: Department of Neuroscience, University of Pennsylvania, PA, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Balice-Gordon
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: iilla@santpau.cat.
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
mesh_terms: D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D051356:Cortactin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009157:Myasthenia Gravis / Q000276:immunology*; D040081:Protein Array Analysis; D011950:Receptors, Cholinergic / Q000276:immunology
chemical_list: D001323:Autoantibodies; C495868:CTTN protein, human; D051356:Cortactin; D011950:Receptors, Cholinergic
keywords: Acetylcholine receptor; Cortactin; Musk; Myasthenia