title: MuSK autoantibodies in myasthenia gravis detected by cell based assay--A multinational study.
abstract: Seronegative myasthenia gravis (MG) presents a serious gap in MG diagnosis and understanding. We applied a cell based assay (CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive. MuSK antibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosed MuSK-MG patients are presented. 27% of ocular seronegative patients were MuSK antibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed.
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece; University of Patras, Patras, Greece.
authors.forename: A I
authors.initials: AI
authors.lastname: Tsonis
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece. Electronic address: zisimopoulou@pasteur.gr.
authors.forename: P
authors.initials: P
authors.lastname: Zisimopoulou
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Lazaridis
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Tzartos
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Matsigkou
authors.affiliation: Neurology Department, Aeginition Hospital, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Zouvelou
authors.affiliation: Neurological Institute "C. Besta", Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mantegazza
authors.affiliation: Neurological Institute "C. Besta", Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Antozzi
authors.affiliation: Neurological Institute "C. Besta", Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Andreetta
authors.affiliation: Institute of Neurology, Catholic University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Evoli
authors.affiliation: Istanbul University, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Deymeer
authors.affiliation: Istanbul University, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.affiliation: Istanbul University, Istanbul, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Durmus
authors.affiliation: Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Brenner
authors.affiliation: Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Vaknin
authors.affiliation: UPMC and INSERM, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Berrih-Aknin
authors.affiliation: UPMC and INSERM, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Behin
authors.affiliation: Raymond Poincaré Hospital, Garches, France.
authors.forename: T
authors.initials: T
authors.lastname: Sharshar
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: De Baets
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Losen
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Martinez-Martinez
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: K A
authors.initials: KA
authors.lastname: Kleopa
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: E
authors.initials: E
authors.lastname: Zamba-Papanicolaou
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: T
authors.initials: T
authors.lastname: Kyriakides
authors.affiliation: Department of Neurology, Medical University of Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kostera-Pruszczyk
authors.affiliation: Department of Neurology, Medical University of Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Szczudlik
authors.affiliation: Department of Neurology, Medical University of Warsaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Szyluk
authors.affiliation: Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Lavrnic
authors.affiliation: Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: I
authors.initials: I
authors.lastname: Basta
authors.affiliation: Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Peric
authors.affiliation: Norway Department of Neurology, Ullevaal University Hospital, Oslo, Norway; Faculty of Medicine, Olso University, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Tallaksen
authors.affiliation: Norway Department of Neurology, Ullevaal University Hospital, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Maniaol
authors.affiliation: Bellvitge University Hospital, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Casasnovas Pons
authors.affiliation: Department of Neurology and Clinical Neuroscience Center, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Pitha
authors.affiliation: Department of Neurology and Clinical Neuroscience Center, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Jakubíkova
authors.affiliation: Universitätsklinikum Halle, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hanisch
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece; University of Patras, Patras, Greece; Tzartos NeuroDiagnostics, Athens, Greece. Electronic address: tzartos@pasteur.gr.
authors.forename: S J
authors.initials: SJ
authors.lastname: Tzartos
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007391:International Cooperation; D026502:LDL-Receptor Related Proteins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D009471:Neuromyelitis Optica / Q000175:diagnosis; D011863:Radioimmunoassay; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology; D013952:Thymus Hyperplasia / Q000175:diagnosis
chemical_list: D001323:Autoantibodies; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D011950:Receptors, Cholinergic; D020794:Receptor Protein-Tyrosine Kinases
keywords: Autoantibodies; Cell based assay; Diagnosis; MuSK; Myasthenia gravis