title: Anti-Hu antibodies activate enteric and sensory neurons.
abstract: IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA. Ca++imaging experiments confirmed activation of enteric neurons but not enteric glia. These findings demonstrate a direct excitatory action of ANNA-1, in particular anti-HuD, on visceral sensory and enteric neurons, which involves nicotinic and P2X receptors. The results provide evidence for a novel link between nerve activation and symptom generation in patients with antibody-mediated gut dysfunction.
authors.affiliation: Human Biology, Technical University of Munich, Freising, Germany.|Department of Physiology, Shandong University School of Medicine, Jinan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Human Biology, Technical University of Munich, Freising, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Michel
authors.affiliation: Human Biology, Technical University of Munich, Freising, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Annahazi
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich; Munich, Germany.
authors.forename: Ihsan E
authors.initials: IE
authors.lastname: Demir
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich; Munich, Germany.
authors.forename: Güralp O
authors.initials: GO
authors.lastname: Ceyhan
authors.affiliation: Surgery, Clinic Freising, Freising, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Zeller
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.affiliation: GI Diseases Research Unit, Queen's University, Kingston, ON, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Beyak
authors.affiliation: Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
authors.forename: David
authors.initials: D
authors.lastname: Grundy
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.affiliation: Department of Medical and Surgical Sciences and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.affiliation: Human Biology, Technical University of Munich, Freising, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schemann
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology; D000067779:ELAV-Like Protein 4 / Q000276:immunology*; D017615:Enteric Nervous System / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011984:Sensory Receptor Cells / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human