Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease

Background and aims: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Metho...

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Veröffentlicht in:Gut 2003-05, Vol.52 (5), p.629-636
Hauptverfasser: Moses, P L, Ellis, L M, Anees, M R, Ho, W, Rothstein, R I, Meddings, J B, Sharkey, K A, Mawe, G M
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container_issue 5
container_start_page 629
container_title Gut
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creator Moses, P L
Ellis, L M
Anees, M R
Ho, W
Rothstein, R I
Meddings, J B
Sharkey, K A
Mawe, G M
description Background and aims: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Methods: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. Results: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p
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We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Methods: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. Results: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p&lt;0.001; GORD, p&lt;0.01), and immunoreactivity was significantly more intense with achalasia and GORD serum samples than controls (achalasia, p&lt;0.01; GORD, p&lt;0.05). There was no correlation between intensity of immunoreactivity and duration of achalasia symptoms. In most cases, achalasia and GORD sera stained all ileal submucosal and myenteric neurones, and oesophageal neurones. Immunostaining was not species specific; however, immunostaining was largely specific for enteric neurones. Western blot analysis failed to reveal specific myenteric neuronal proteins that were labelled by antibodies in achalasia or GORD serum. Conclusions: These data suggest that antineuronal antibodies are generated in response to tissue damage or some other secondary phenomenon in achalasia and GORD. We conclude that antineuronal antibodies found in the serum of patients with achalasia represent an epiphenomenon and not a causative factor.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>EISSN: 1458-3288</identifier><identifier>DOI: 10.1136/gut.52.5.629</identifier><identifier>PMID: 12692044</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Achalasia ; Animals ; Antibodies - analysis ; autoantibodies ; autoimmune ; Biological and medical sciences ; Blotting, Western - methods ; Cell Nucleus - immunology ; Development and progression ; Dysphagia ; enteric nervous system ; Esophageal Achalasia - immunology ; Esophagus ; Esophagus - immunology ; FITC ; fluorescein isothiocyanate ; Fluorescent Antibody Technique - methods ; gastro-oesophageal reflux disease ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastroesophageal reflux ; Gastroesophageal Reflux - immunology ; GORD ; Guinea Pigs ; Humans ; Ileum - immunology ; Immunoglobulins ; Intestinal Mucosa - immunology ; Labeling ; LMMP ; longitudinal muscle-myenteric plexus ; LOS ; lower oesophageal sphincter ; Medical sciences ; Mice ; Motility ; Myenteric Plexus - immunology ; neurogastroenterology ; Neurons - immunology ; nitric oxide synthase ; NOS ; oesophageal motility ; Oesophagus ; Other diseases. Semiology ; PBS ; phosphate buffered saline ; Physiological aspects ; Proteins - immunology ; Risk factors ; Rodents ; Species Specificity ; Studies ; TBS-T ; Tris buffered saline with 0.05% Tween-20</subject><ispartof>Gut, 2003-05, Vol.52 (5), p.629-636</ispartof><rights>Copyright 2003 by Gut</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 BMJ Publishing Group Ltd.</rights><rights>Copyright: 2003 Copyright 2003 by Gut</rights><rights>Copyright © Copyright 2003 by Gut 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b613t-6f2cacacc41c2a0f8b47bff7c45701794ac308048d92b17e150ca6994ba256be3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773656/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773656/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=14699762$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12692044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moses, P L</creatorcontrib><creatorcontrib>Ellis, L M</creatorcontrib><creatorcontrib>Anees, M R</creatorcontrib><creatorcontrib>Ho, W</creatorcontrib><creatorcontrib>Rothstein, R I</creatorcontrib><creatorcontrib>Meddings, J B</creatorcontrib><creatorcontrib>Sharkey, K A</creatorcontrib><creatorcontrib>Mawe, G M</creatorcontrib><title>Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease</title><title>Gut</title><addtitle>Gut</addtitle><description>Background and aims: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Methods: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. Results: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p&lt;0.001; GORD, p&lt;0.01), and immunoreactivity was significantly more intense with achalasia and GORD serum samples than controls (achalasia, p&lt;0.01; GORD, p&lt;0.05). There was no correlation between intensity of immunoreactivity and duration of achalasia symptoms. In most cases, achalasia and GORD sera stained all ileal submucosal and myenteric neurones, and oesophageal neurones. Immunostaining was not species specific; however, immunostaining was largely specific for enteric neurones. Western blot analysis failed to reveal specific myenteric neuronal proteins that were labelled by antibodies in achalasia or GORD serum. Conclusions: These data suggest that antineuronal antibodies are generated in response to tissue damage or some other secondary phenomenon in achalasia and GORD. We conclude that antineuronal antibodies found in the serum of patients with achalasia represent an epiphenomenon and not a causative factor.</description><subject>Achalasia</subject><subject>Animals</subject><subject>Antibodies - analysis</subject><subject>autoantibodies</subject><subject>autoimmune</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western - methods</subject><subject>Cell Nucleus - immunology</subject><subject>Development and progression</subject><subject>Dysphagia</subject><subject>enteric nervous system</subject><subject>Esophageal Achalasia - immunology</subject><subject>Esophagus</subject><subject>Esophagus - immunology</subject><subject>FITC</subject><subject>fluorescein isothiocyanate</subject><subject>Fluorescent Antibody Technique - methods</subject><subject>gastro-oesophageal reflux disease</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gastroesophageal reflux</subject><subject>Gastroesophageal Reflux - immunology</subject><subject>GORD</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>Ileum - immunology</subject><subject>Immunoglobulins</subject><subject>Intestinal Mucosa - immunology</subject><subject>Labeling</subject><subject>LMMP</subject><subject>longitudinal muscle-myenteric plexus</subject><subject>LOS</subject><subject>lower oesophageal sphincter</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Motility</subject><subject>Myenteric Plexus - immunology</subject><subject>neurogastroenterology</subject><subject>Neurons - immunology</subject><subject>nitric oxide synthase</subject><subject>NOS</subject><subject>oesophageal motility</subject><subject>Oesophagus</subject><subject>Other diseases. Semiology</subject><subject>PBS</subject><subject>phosphate buffered saline</subject><subject>Physiological aspects</subject><subject>Proteins - immunology</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Species Specificity</subject><subject>Studies</subject><subject>TBS-T</subject><subject>Tris buffered saline with 0.05% Tween-20</subject><issn>0017-5749</issn><issn>1468-3288</issn><issn>1458-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9ksuP0zAQhyMEYpeFG2cUCQEXUvy2c0EqXV5iBZddOFoTx0ldUrvYCVr-e1xabVlUoTlY9nzz87yK4jFGM4ypeNVP44yTGZ8JUt8pTjETqqJEqbvFKUJYVlyy-qR4kNIKIaRUje8XJ5iImiDGTouruR-dt1MMHoYS8qUJrbOpdL50rQsbGJfOlGCWMEBykJG27CGNMVTBprBZQm9zZLTdMF2XrUsWkn1Y3OtgSPbR_jwrrt69vVx8qC6-vP-4mF9UjcB0rERHDGQzDBsCqFMNk03XScO4zKnXDAxFCjHV1qTB0mKODIi6Zg0QLhpLz4rXO93N1Kxta6wfIwx6E90a4i8dwOnbHu-Wug8_NZaSCi6ywPO9QAw_JptGvXbJ2GEAb8OUtKRYUa7qDD79B1yFKeaepa1WTQmqBTlQPQxWO9-F_KvZSuo5RphSoYjMVHWE6q23OcXgbefy8y1-doTP1tq1M0cDXu4CTAwp5dHcdAQjvV0anZdGc6K5zkuT8Sd_d_EA77ckA8_2ACQDQxfBG5cOHMszkX_K3xfm0mivb_wQv2shqeT689eF_vTtnF8yca7fZP7Fjm_Wq_-n-BuT6OWw</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>Moses, P L</creator><creator>Ellis, L M</creator><creator>Anees, M R</creator><creator>Ho, W</creator><creator>Rothstein, R I</creator><creator>Meddings, J B</creator><creator>Sharkey, K A</creator><creator>Mawe, G M</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ</general><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>Copyright 2003 by Gut</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030501</creationdate><title>Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease</title><author>Moses, P L ; Ellis, L M ; Anees, M R ; Ho, W ; Rothstein, R I ; Meddings, J B ; Sharkey, K A ; Mawe, G M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b613t-6f2cacacc41c2a0f8b47bff7c45701794ac308048d92b17e150ca6994ba256be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Achalasia</topic><topic>Animals</topic><topic>Antibodies - analysis</topic><topic>autoantibodies</topic><topic>autoimmune</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western - methods</topic><topic>Cell Nucleus - immunology</topic><topic>Development and progression</topic><topic>Dysphagia</topic><topic>enteric nervous system</topic><topic>Esophageal Achalasia - immunology</topic><topic>Esophagus</topic><topic>Esophagus - immunology</topic><topic>FITC</topic><topic>fluorescein isothiocyanate</topic><topic>Fluorescent Antibody Technique - methods</topic><topic>gastro-oesophageal reflux disease</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gastroesophageal reflux</topic><topic>Gastroesophageal Reflux - immunology</topic><topic>GORD</topic><topic>Guinea Pigs</topic><topic>Humans</topic><topic>Ileum - immunology</topic><topic>Immunoglobulins</topic><topic>Intestinal Mucosa - immunology</topic><topic>Labeling</topic><topic>LMMP</topic><topic>longitudinal muscle-myenteric plexus</topic><topic>LOS</topic><topic>lower oesophageal sphincter</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Motility</topic><topic>Myenteric Plexus - immunology</topic><topic>neurogastroenterology</topic><topic>Neurons - immunology</topic><topic>nitric oxide synthase</topic><topic>NOS</topic><topic>oesophageal motility</topic><topic>Oesophagus</topic><topic>Other diseases. Semiology</topic><topic>PBS</topic><topic>phosphate buffered saline</topic><topic>Physiological aspects</topic><topic>Proteins - immunology</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Species Specificity</topic><topic>Studies</topic><topic>TBS-T</topic><topic>Tris buffered saline with 0.05% Tween-20</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moses, P L</creatorcontrib><creatorcontrib>Ellis, L M</creatorcontrib><creatorcontrib>Anees, M R</creatorcontrib><creatorcontrib>Ho, W</creatorcontrib><creatorcontrib>Rothstein, R I</creatorcontrib><creatorcontrib>Meddings, J B</creatorcontrib><creatorcontrib>Sharkey, K A</creatorcontrib><creatorcontrib>Mawe, G M</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moses, P L</au><au>Ellis, L M</au><au>Anees, M R</au><au>Ho, W</au><au>Rothstein, R I</au><au>Meddings, J B</au><au>Sharkey, K A</au><au>Mawe, G M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>52</volume><issue>5</issue><spage>629</spage><epage>636</epage><pages>629-636</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><eissn>1458-3288</eissn><coden>GUTTAK</coden><abstract>Background and aims: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Methods: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. Results: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p&lt;0.001; GORD, p&lt;0.01), and immunoreactivity was significantly more intense with achalasia and GORD serum samples than controls (achalasia, p&lt;0.01; GORD, p&lt;0.05). There was no correlation between intensity of immunoreactivity and duration of achalasia symptoms. In most cases, achalasia and GORD sera stained all ileal submucosal and myenteric neurones, and oesophageal neurones. Immunostaining was not species specific; however, immunostaining was largely specific for enteric neurones. Western blot analysis failed to reveal specific myenteric neuronal proteins that were labelled by antibodies in achalasia or GORD serum. Conclusions: These data suggest that antineuronal antibodies are generated in response to tissue damage or some other secondary phenomenon in achalasia and GORD. We conclude that antineuronal antibodies found in the serum of patients with achalasia represent an epiphenomenon and not a causative factor.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>12692044</pmid><doi>10.1136/gut.52.5.629</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects Achalasia
Animals
Antibodies - analysis
autoantibodies
autoimmune
Biological and medical sciences
Blotting, Western - methods
Cell Nucleus - immunology
Development and progression
Dysphagia
enteric nervous system
Esophageal Achalasia - immunology
Esophagus
Esophagus - immunology
FITC
fluorescein isothiocyanate
Fluorescent Antibody Technique - methods
gastro-oesophageal reflux disease
Gastroenterology. Liver. Pancreas. Abdomen
Gastroesophageal reflux
Gastroesophageal Reflux - immunology
GORD
Guinea Pigs
Humans
Ileum - immunology
Immunoglobulins
Intestinal Mucosa - immunology
Labeling
LMMP
longitudinal muscle-myenteric plexus
LOS
lower oesophageal sphincter
Medical sciences
Mice
Motility
Myenteric Plexus - immunology
neurogastroenterology
Neurons - immunology
nitric oxide synthase
NOS
oesophageal motility
Oesophagus
Other diseases. Semiology
PBS
phosphate buffered saline
Physiological aspects
Proteins - immunology
Risk factors
Rodents
Species Specificity
Studies
TBS-T
Tris buffered saline with 0.05% Tween-20
title Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease
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