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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)
Author(s) -
Hubball A. W.,
Lang B.,
Souza M. A. N.,
Curran O. D.,
Martin J. E.,
Knowles C. H.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2012.01924.x
Subject(s) - autoantibody , enteric nervous system , antibody , medicine , immunology , esophagus , myenteric plexus , gastroenterology , biology , pathology , immunohistochemistry
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; α 3 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. Key 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 & Inferences 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.