title: Potassium channel KIR4.1-specific antibodies in children with acquired demyelinating CNS disease.
abstract: OBJECTIVE
  A serum antibody against the inward rectifying potassium channel KIR4.1 (KIR4.1-IgG) was recently discovered, which is found in almost half of adult patients with multiple sclerosis. We investigated the prevalence of KIR4.1-IgG in children with acquired demyelinating disease (ADD) of the CNS. We also compared antibody responses to KIR4.1 and myelin oligodendrocyte glycoproteins (MOGs), another potential autoantigen in childhood ADDs.
  
  
  METHODS
  We measured KIR4.1-IgG by ELISA in children with ADD (n = 47), other neurologic disease (n = 22), and autoimmune disease (n = 22), and in healthy controls (HCs) (n = 18). One hundred six samples were also measured by capture ELISA. Binding of KIR4.1-IgG human subcortical white matter was analyzed by immunofluorescence. Anti-MOG antibodies were measured using a cell-based assay.
  
  
  RESULTS
  KIR4.1-IgG titers were significantly higher in children with ADD compared with all control groups by ELISA and capture ELISA (p < 0.0001, p < 0.0001). Overall, 27 of 47 patients with ADD (57.45%) but none of the 62 with other neurologic disease or autoimmune disease or the HCs (0%) were KIR4.1-IgG antibody positive by ELISA. Sera containing KIR4.1-IgG stained glial cells in brain tissue sections. No correlation among KIR4.1-IgG, age, or MOG-IgG was observed in the ADD group.
  
  
  CONCLUSIONS
  Serum antibodies to KIR4.1 are found in the majority of children with ADD but not in children with other diseases or in HCs. These findings suggest that KIR4.1 is an important target of autoantibodies in childhood ADD.
authors.affiliation: From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Kraus
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Srivastava
authors.forename: Sudhakar Reddy
authors.initials: SR
authors.lastname: Kalluri
authors.forename: Ulrich
authors.initials: U
authors.lastname: Seidel
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Mareike
authors.initials: M
authors.lastname: Schimmel
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Steffen
authors.initials: S
authors.lastname: Leiz
authors.forename: Stuart
authors.initials: S
authors.lastname: Hosie
authors.forename: Verena
authors.initials: V
authors.lastname: Grummel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D001921:Brain / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009413:Nerve Fibers, Myelinated / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology; D024661:Potassium Channels, Inwardly Rectifying / Q000276:immunology*; D000098854:Kcnj10 Channel
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D000098854:Kcnj10 Channel; C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein; D024661:Potassium Channels, Inwardly Rectifying