Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

Background Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. Methods The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using...

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Published in:Journal of gastroenterology 2023-08, Vol.58 (8), p.778-789
Main Authors: Yoshida, Hiroyuki, Shiokawa, Masahiro, Kuwada, Takeshi, Muramoto, Yuya, Ota, Sakiko, Nishikawa, Yoshihiro, Maeda, Hirona, Kakiuchi, Nobuyuki, Okamoto, Kanako, Yamazaki, Hajime, Yokode, Masataka, Nakamura, Takeharu, Matsumoto, Shimpei, Hirano, Tomonori, Okada, Hirokazu, Marui, Saiko, Sogabe, Yuko, Matsumori, Tomoaki, Mima, Atsushi, Uza, Norimitsu, Eso, Yuji, Takai, Atsushi, Takahashi, Ken, Ueda, Yoshihide, Kodama, Yuzo, Chiba, Tsutomu, Seno, Hiroshi
Format: Article
Language:English
Subjects:
Abdominal Surgery
Autoantibodies
Bile ducts
Biliary Tract
Cholangitis
Cholangitis, Sclerosing
Colorectal Surgery
Enzyme-Linked Immunosorbent Assay
Epithelial cells
Epithelial Cells - metabolism
Fibronectin
Gastroenterology
Hepatology
Humans
Immunofluorescence
Immunoglobulins
Inflammatory Bowel Diseases
Medicine
Medicine & Public Health
Original Article―Liver
Original ―Liver, Pancreas, and Biliary Tract
Pancreas
Surgical Oncology
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cited_by cdi_FETCH-LOGICAL-c543t-4083ea6564068bd1b76f993a69b95855d94cfd002f5dad27b69ed502af41f88a3
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creator Yoshida, Hiroyuki
Shiokawa, Masahiro
Kuwada, Takeshi
Muramoto, Yuya
Ota, Sakiko
Nishikawa, Yoshihiro
Maeda, Hirona
Kakiuchi, Nobuyuki
Okamoto, Kanako
Yamazaki, Hajime
Yokode, Masataka
Nakamura, Takeharu
Matsumoto, Shimpei
Hirano, Tomonori
Okada, Hirokazu
Marui, Saiko
Sogabe, Yuko
Matsumori, Tomoaki
Mima, Atsushi
Uza, Norimitsu
Eso, Yuji
Takai, Atsushi
Takahashi, Ken
Ueda, Yoshihide
Kodama, Yuzo
Chiba, Tsutomu
Seno, Hiroshi
description Background Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. Methods The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. Results Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls ( P  
doi_str_mv 10.1007/s00535-023-02006-6
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However, the target molecules remain unknown. Methods The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. Results Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls ( P  &lt; 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) ( P  = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif. Conclusions Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-023-02006-6</identifier><identifier>PMID: 37310456</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Abdominal Surgery ; Autoantibodies ; Bile ducts ; Biliary Tract ; Cholangitis ; Cholangitis, Sclerosing ; Colorectal Surgery ; Enzyme-Linked Immunosorbent Assay ; Epithelial cells ; Epithelial Cells - metabolism ; Fibronectin ; Gastroenterology ; Hepatology ; Humans ; Immunofluorescence ; Immunoglobulins ; Inflammatory Bowel Diseases ; Medicine ; Medicine &amp; Public Health ; Original Article―Liver ; Original ―Liver, Pancreas, and Biliary Tract ; Pancreas ; Surgical Oncology</subject><ispartof>Journal of gastroenterology, 2023-08, Vol.58 (8), p.778-789</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-4083ea6564068bd1b76f993a69b95855d94cfd002f5dad27b69ed502af41f88a3</citedby><cites>FETCH-LOGICAL-c543t-4083ea6564068bd1b76f993a69b95855d94cfd002f5dad27b69ed502af41f88a3</cites><orcidid>0000-0002-1551-8721</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37310456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshida, Hiroyuki</creatorcontrib><creatorcontrib>Shiokawa, Masahiro</creatorcontrib><creatorcontrib>Kuwada, Takeshi</creatorcontrib><creatorcontrib>Muramoto, Yuya</creatorcontrib><creatorcontrib>Ota, Sakiko</creatorcontrib><creatorcontrib>Nishikawa, Yoshihiro</creatorcontrib><creatorcontrib>Maeda, Hirona</creatorcontrib><creatorcontrib>Kakiuchi, Nobuyuki</creatorcontrib><creatorcontrib>Okamoto, Kanako</creatorcontrib><creatorcontrib>Yamazaki, Hajime</creatorcontrib><creatorcontrib>Yokode, Masataka</creatorcontrib><creatorcontrib>Nakamura, Takeharu</creatorcontrib><creatorcontrib>Matsumoto, Shimpei</creatorcontrib><creatorcontrib>Hirano, Tomonori</creatorcontrib><creatorcontrib>Okada, Hirokazu</creatorcontrib><creatorcontrib>Marui, Saiko</creatorcontrib><creatorcontrib>Sogabe, Yuko</creatorcontrib><creatorcontrib>Matsumori, Tomoaki</creatorcontrib><creatorcontrib>Mima, Atsushi</creatorcontrib><creatorcontrib>Uza, Norimitsu</creatorcontrib><creatorcontrib>Eso, Yuji</creatorcontrib><creatorcontrib>Takai, Atsushi</creatorcontrib><creatorcontrib>Takahashi, Ken</creatorcontrib><creatorcontrib>Ueda, Yoshihide</creatorcontrib><creatorcontrib>Kodama, Yuzo</creatorcontrib><creatorcontrib>Chiba, Tsutomu</creatorcontrib><creatorcontrib>Seno, Hiroshi</creatorcontrib><title>Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. Methods The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. Results Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls ( P  &lt; 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) ( P  = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif. Conclusions Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC.</description><subject>Abdominal Surgery</subject><subject>Autoantibodies</subject><subject>Bile ducts</subject><subject>Biliary Tract</subject><subject>Cholangitis</subject><subject>Cholangitis, Sclerosing</subject><subject>Colorectal Surgery</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Fibronectin</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunoglobulins</subject><subject>Inflammatory Bowel Diseases</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Original Article―Liver</subject><subject>Original ―Liver, Pancreas, and Biliary Tract</subject><subject>Pancreas</subject><subject>Surgical Oncology</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kctO3DAYhS1EVYZpX6CLKhIbNim_r4lXFUJAKyGxaLu2nMTJGGXswXZAPBY8CM-Eh5ly6aILy5LP5_NfDkJfMHzDANVRBOCUl0BoPgCiFDtohll-4pKQXTQDyViJccX20H6MVwCYAq8_oj1aUQyMixn6deySLa1LZgjWFY_3N48PotBT8joLje-siUUWVjpZ41Isbm1aFKtglzrcFbEdTfDRuqFoF37UbrDJxk_oQ6_HaD5v7zn6c3b6--RHeXF5_vPk-KJsOaOpZFBTowUXDETddLipRC8l1UI2ktecd5K1fQdAet7pjlSNkKbjQHTPcF_Xms7R943vamqWpmtzf0GPatuc8tqq94qzCzX4G4WBCkHzpubocOsQ_PVkYlJLG1sz5kmMn6IiNeG5Iq3X6ME_6JWfgsvzZUpmQybomiIbqs1ricH0L91gUOvQ1CY0lU3Vc2hK5E9f387x8uVvShmgGyBmyQ0mvNb-j-0TrTukyg</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Yoshida, Hiroyuki</creator><creator>Shiokawa, Masahiro</creator><creator>Kuwada, Takeshi</creator><creator>Muramoto, Yuya</creator><creator>Ota, Sakiko</creator><creator>Nishikawa, Yoshihiro</creator><creator>Maeda, Hirona</creator><creator>Kakiuchi, Nobuyuki</creator><creator>Okamoto, Kanako</creator><creator>Yamazaki, Hajime</creator><creator>Yokode, Masataka</creator><creator>Nakamura, Takeharu</creator><creator>Matsumoto, Shimpei</creator><creator>Hirano, Tomonori</creator><creator>Okada, Hirokazu</creator><creator>Marui, Saiko</creator><creator>Sogabe, Yuko</creator><creator>Matsumori, Tomoaki</creator><creator>Mima, Atsushi</creator><creator>Uza, Norimitsu</creator><creator>Eso, Yuji</creator><creator>Takai, Atsushi</creator><creator>Takahashi, Ken</creator><creator>Ueda, Yoshihide</creator><creator>Kodama, Yuzo</creator><creator>Chiba, Tsutomu</creator><creator>Seno, Hiroshi</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>C6C</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>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1551-8721</orcidid></search><sort><creationdate>20230801</creationdate><title>Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis</title><author>Yoshida, Hiroyuki ; Shiokawa, Masahiro ; Kuwada, Takeshi ; Muramoto, Yuya ; Ota, Sakiko ; Nishikawa, Yoshihiro ; Maeda, Hirona ; Kakiuchi, Nobuyuki ; Okamoto, Kanako ; Yamazaki, Hajime ; Yokode, Masataka ; Nakamura, Takeharu ; Matsumoto, Shimpei ; Hirano, Tomonori ; Okada, Hirokazu ; Marui, Saiko ; Sogabe, Yuko ; Matsumori, Tomoaki ; Mima, Atsushi ; Uza, Norimitsu ; Eso, Yuji ; Takai, Atsushi ; Takahashi, Ken ; Ueda, Yoshihide ; Kodama, Yuzo ; Chiba, Tsutomu ; Seno, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-4083ea6564068bd1b76f993a69b95855d94cfd002f5dad27b69ed502af41f88a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Abdominal Surgery</topic><topic>Autoantibodies</topic><topic>Bile ducts</topic><topic>Biliary Tract</topic><topic>Cholangitis</topic><topic>Cholangitis, Sclerosing</topic><topic>Colorectal Surgery</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Fibronectin</topic><topic>Gastroenterology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunoglobulins</topic><topic>Inflammatory Bowel Diseases</topic><topic>Medicine</topic><topic>Medicine &amp; 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However, the target molecules remain unknown. Methods The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. Results Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls ( P  &lt; 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) ( P  = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif. Conclusions Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>37310456</pmid><doi>10.1007/s00535-023-02006-6</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1551-8721</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0944-1174
ispartof Journal of gastroenterology, 2023-08, Vol.58 (8), p.778-789
issn 0944-1174
1435-5922
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10366314
source Springer Nature
subjects Abdominal Surgery
Autoantibodies
Bile ducts
Biliary Tract
Cholangitis
Cholangitis, Sclerosing
Colorectal Surgery
Enzyme-Linked Immunosorbent Assay
Epithelial cells
Epithelial Cells - metabolism
Fibronectin
Gastroenterology
Hepatology
Humans
Immunofluorescence
Immunoglobulins
Inflammatory Bowel Diseases
Medicine
Medicine & Public Health
Original Article―Liver
Original ―Liver, Pancreas, and Biliary Tract
Pancreas
Surgical Oncology
title Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T15%3A59%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Anti-integrin%20%CE%B1v%CE%B26%20autoantibodies%20in%20patients%20with%20primary%20sclerosing%20cholangitis&rft.jtitle=Journal%20of%20gastroenterology&rft.au=Yoshida,%20Hiroyuki&rft.date=2023-08-01&rft.volume=58&rft.issue=8&rft.spage=778&rft.epage=789&rft.pages=778-789&rft.issn=0944-1174&rft.eissn=1435-5922&rft_id=info:doi/10.1007/s00535-023-02006-6&rft_dat=%3Cproquest_pubme%3E2825502384%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c543t-4083ea6564068bd1b76f993a69b95855d94cfd002f5dad27b69ed502af41f88a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2890364634&rft_id=info:pmid/37310456&rfr_iscdi=true