title: Clinical relevance of voltage-gated  potassium channel–complex antibodies  in children.
abstract: OBJECTIVE
  To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs).
  
  
  METHODS
  Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients’ condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins.
  
  
  RESULTS
  VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells.
  
  
  CONCLUSIONS
  Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.
authors: Yael
authors: Y
authors: Hacohen
authors: Rahul
authors: R
authors: Singh
authors: Meghan
authors: M
authors: Rossi
authors: Bethan
authors: B
authors: Lang
authors: Cheryl
authors: C
authors: Hemingway
authors: Ming
authors: M
authors: Lim
authors: Angela
authors: A
authors: Vincent
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000276:immunology; D009474:Neurons / Q000276:immunology; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011506:Proteins / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; C033652:postsynaptic density proteins