title: Voltage-gated potassium channel (K(v) 1) autoantibodies in patients with chagasic gut dysmotility and distribution of K(v) 1 channels in human enteric neuromusculature (autoantibodies in GI dysmotility).
abstract: BACKGROUND
  Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs) was also investigated.
  
  
  METHODS
  Seventy-three patients were included in the study with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas' disease. Sera were screened for specific antibodies to glutamic acid decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic acetylcholine receptors (nAChRs; α3 subtype), and voltage-gated potassium channels (VGKCs, K(V) 1 subtype) using validated immunoprecipitation assays. The distribution of six VGKC subunits (K(V) 1.1-1.6), including those known to be antigenic targets of anti-VGKC antibodies was immunohistochemically investigated in all main human GI tract regions.
  
  
  RESULTS
  Three patients (14%) with chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No antibodies were detected in patients with idiopathic GINMD. The VGKCs were found in enteric neurons at every level of the gut in unique yet overlapping distributions. The VGKC expression in GI smooth muscle was found to be limited to the esophagus.
  
  
  CONCLUSIONS
  A small proportion of patients with GI dysfunction secondary to Chagas' disease have antibodies against VGKCs. The presence of these channels in the human enteric nervous system may have pathological relevance to the growing number of GINMDs with which anti-VGKC antibodies have been associated.
authors.affiliation: Wingate Institute for Neurogastroenterology, Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University London, London, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Hubball
authors.forename: B
authors.initials: B
authors.lastname: Lang
authors.forename: M A N
authors.initials: MA
authors.lastname: Souza
authors.forename: O D
authors.initials: OD
authors.lastname: Curran
authors.forename: J E
authors.initials: JE
authors.lastname: Martin
authors.forename: C H
authors.initials: CH
authors.lastname: Knowles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D014355:Chagas Disease / Q000150:complications / Q000276:immunology*; D004066:Digestive System Diseases / Q000209:etiology / Q000276:immunology*; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D051637:Shaker Superfamily of Potassium Channels / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D051637:Shaker Superfamily of Potassium Channels