PMID- 25193850 OWN - NLM STAT- MEDLINE DCOM- 20141125 LR - 20181202 IS - 1873-0183 (Electronic) IS - 1568-9972 (Linking) VI - 13 IP - 10 DP - 2014 Oct TI - Cortactin autoantibodies in myasthenia gravis. PG - 1003-7 LID - S1568-9972(14)00183-9 [pii] LID - 10.1016/j.autrev.2014.08.039 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Gallardo, Eduard AU - Gallardo E AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Martinez-Hernandez, Eugenia AU - Martinez-Hernandez E AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Titulaer, Maarten J AU - Titulaer MJ AD - Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. FAU - Huijbers, Maartje G AU - Huijbers MG AD - Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Martinez, Maria Angeles AU - Martinez MA AD - Department of Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Ramos, Alba AU - Ramos A AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Querol, Luis AU - Querol L AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Diaz-Manera, Jordi AU - Diaz-Manera J AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Rojas-Garcia, Ricard AU - Rojas-Garcia R AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Hayworth, Christopher R AU - Hayworth CR AD - Department of Neuroscience, University of Pennsylvania, PA, USA. FAU - Verschuuren, Jan J AU - Verschuuren JJ AD - Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Balice-Gordon, Rita AU - Balice-Gordon R AD - Department of Neuroscience, University of Pennsylvania, PA, USA. FAU - Dalmau, Josep AU - Dalmau J AD - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain. FAU - Illa, Isabel AU - Illa I AD - Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: iilla@santpau.cat. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140903 PL - Netherlands TA - Autoimmun Rev JT - Autoimmunity reviews JID - 101128967 RN - 0 (Autoantibodies) RN - 0 (CTTN protein, human) RN - 0 (Cortactin) RN - 0 (Receptors, Cholinergic) SB - IM MH - Autoantibodies/*analysis/immunology MH - Cortactin/immunology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Male MH - Myasthenia Gravis/*immunology MH - Protein Array Analysis MH - Receptors, Cholinergic/immunology OTO - NOTNLM OT - Acetylcholine receptor OT - Cortactin OT - Musk OT - Myasthenia EDAT- 2014/09/07 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/09/07 06:00 PHST- 2014/06/19 00:00 [received] PHST- 2014/06/25 00:00 [accepted] PHST- 2014/09/07 06:00 [entrez] PHST- 2014/09/07 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S1568-9972(14)00183-9 [pii] AID - 10.1016/j.autrev.2014.08.039 [doi] PST - ppublish SO - Autoimmun Rev. 2014 Oct;13(10):1003-7. doi: 10.1016/j.autrev.2014.08.039. Epub 2014 Sep 3.