title: Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity.
abstract: Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies.
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands. Electronic address: M.G.M.Huijbers@lumc.nl.
authors: Maartje G
authors: MG
authors: Huijbers
authors: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Anna-Fleur D
authors: AF
authors: Vink
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Erik H
authors: EH
authors: Niks
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Ruben H
authors: RH
authors: Westhuis
authors: Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Erik W
authors: EW
authors: van Zwet
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Robert H
authors: RH
authors: de Meel
authors: Department of Neurology, Hospital Santa Creu I Sant Pau, Barcelona, Spain.
authors: Ricardo
authors: R
authors: Rojas-García
authors: Department of Neurology, Hospital Santa Creu I Sant Pau, Barcelona, Spain.
authors: Jordi
authors: J
authors: Díaz-Manera
authors: Department of Neurology, University Medical Centre Groningen, Groningen, The Netherlands.
authors: Jan B
authors: JB
authors: Kuks
authors: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Rinse
authors: R
authors: Klooster
authors: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Kirsten
authors: K
authors: Straasheijm
authors: Department of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Amelia
authors: A
authors: Evoli
authors: Department of Neurology, Hospital Santa Creu I Sant Pau, Barcelona, Spain.
authors: Isabel
authors: I
authors: Illa
authors: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Silvère M
authors: SM
authors: van der Maarel
authors: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Jan J
authors: JJ
authors: Verschuuren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D012720:Severity of Illness Index; D013030:Spain; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Epitope mapping; IgG4; MuSK; Myasthenia gravis; Neuromuscular junction