Anti-Hu antibodies activate enteric and sensory neurons

Qin Li; Klaus Michel; Anita Annahazi; Ihsan E. Demir; Güralp O. Ceyhan; Florian Zeller; Lars Komorowski; Winfried Stöcker; Michael J. Beyak; David Grundy; Gianrico Farrugia; Roberto De Giorgio; Michael Schemann

doi:10.1038/srep38216

Anti-Hu antibodies activate enteric and sensory neurons

Qin Li, Klaus Michel, Anita Annahazi, Ihsan E. Demir, Güralp O. Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J. Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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-HT₃ antagonist 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.

Original language	English
Article number	38216
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep38216
State	Published - 1 Dec 2016

Access to Document

10.1038/srep38216

Cite this

@article{33846ebf1ecf4850992253de25899da4,

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-HT3 antagonist 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.",

author = "Qin Li and Klaus Michel and Anita Annahazi and Demir, {Ihsan E.} and Ceyhan, {G{\"u}ralp O.} and Florian Zeller and Lars Komorowski and Winfried St{\"o}cker and Beyak, {Michael J.} and David Grundy and Gianrico Farrugia and {De Giorgio}, Roberto and Michael Schemann",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = dec,

day = "1",

doi = "10.1038/srep38216",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Anti-Hu antibodies activate enteric and sensory neurons

AU - Li, Qin

AU - Michel, Klaus

AU - Annahazi, Anita

AU - Demir, Ihsan E.

AU - Ceyhan, Güralp O.

AU - Zeller, Florian

AU - Komorowski, Lars

AU - Stöcker, Winfried

AU - Beyak, Michael J.

AU - Grundy, David

AU - Farrugia, Gianrico

AU - De Giorgio, Roberto

AU - Schemann, Michael

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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-HT3 antagonist 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.

AB - 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-HT3 antagonist 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.

UR - http://www.scopus.com/inward/record.url?scp=84999652081&partnerID=8YFLogxK

U2 - 10.1038/srep38216

DO - 10.1038/srep38216

M3 - Article

C2 - 27905561

AN - SCOPUS:84999652081

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 38216

ER -

Anti-Hu antibodies activate enteric and sensory neurons

Abstract

Access to Document

Other files and links

Fingerprint

Cite this