title: MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.
abstract: Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis.
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research, University of Istanbul, Istanbul 34393, Turkey; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Melike
authors.initials: M
authors.lastname: Küçükerden
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ruksana
authors.initials: R
authors.lastname: Huda
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research, University of Istanbul, Istanbul 34393, Turkey. Electronic address: drerdem@yahoo.com.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.affiliation: Department of Immunology, Institute for Experimental Medical Research, University of Istanbul, Istanbul 34393, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Yılmaz
authors.affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Patras 26504, Greece; Hellenic Pasteur Institute, Athens 115 21, Greece.
authors.forename: Lamprini
authors.initials: L
authors.lastname: Skriapa
authors.affiliation: Hellenic Pasteur Institute, Athens 115 21, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Trakas
authors.affiliation: Department of Pediatrics and Cincinnati Children's Hospital Division of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Strait
authors.affiliation: Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45229, USA; Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research, University of Istanbul, Istanbul 34393, Turkey.
authors.forename: Sevil
authors.initials: S
authors.lastname: Kabadayı
authors.affiliation: Hellenic Pasteur Institute, Athens 115 21, Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Zisimopoulou
authors.affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Patras 26504, Greece; Hellenic Pasteur Institute, Athens 115 21, Greece.
authors.forename: Socrates
authors.initials: S
authors.lastname: Tzartos
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Immune Globe Biotech, LLC, 3008 Sea Pines Place, League City, TX 77573, USA.
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000633:toxicity; D007114:Immunization; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D009469:Neuromuscular Junction / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000633:toxicity*; D011950:Receptors, Cholinergic; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D005620:Freund's Adjuvant; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anti-MuSK IgG; Experimental autoimmune myasthenia gravis; MuSK-binding B cell; Muscle specific kinase; Myasthenia gravis