Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease

Abstract Background Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titer and mild enteropathy. Aim We expl...

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Veröffentlicht in:Digestive and liver disease 2016-11, Vol.48 (11), p.1290-1295
Hauptverfasser: Das, Prasenjit, Gahlot, Gaurav P.S, Mehta, Ritu, Makharia, Archita, Verma, Anil K, Sreenivas, V, Panda, Subrat K, Ahuja, Vineet, Gupta, Siddhartha Datta, Makharia, Govind K
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container_end_page 1295
container_issue 11
container_start_page 1290
container_title Digestive and liver disease
container_volume 48
creator Das, Prasenjit
Gahlot, Gaurav P.S
Mehta, Ritu
Makharia, Archita
Verma, Anil K
Sreenivas, V
Panda, Subrat K
Ahuja, Vineet
Gupta, Siddhartha Datta
Makharia, Govind K
description Abstract Background Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titer and mild enteropathy. Aim We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Methods Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 &1) (n = 26), advanced enteropathy (Marsh grade ≥2) (n = 41) and control biopsies (n = 12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. Results End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labeling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Conclusions Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.
doi_str_mv 10.1016/j.dld.2016.06.013
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Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titer and mild enteropathy. Aim We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Methods Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 &amp;1) (n = 26), advanced enteropathy (Marsh grade ≥2) (n = 41) and control biopsies (n = 12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. Results End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labeling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Conclusions Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.</description><identifier>ISSN: 1590-8658</identifier><identifier>EISSN: 1878-3562</identifier><identifier>DOI: 10.1016/j.dld.2016.06.013</identifier><identifier>PMID: 27378705</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Advanced enteropathy ; Apoptosis ; Biomarkers - metabolism ; Biopsy ; Celiac disease ; Celiac Disease - pathology ; Cell Proliferation ; Cross-Sectional Studies ; Crypt regeneration ; Duodenum - pathology ; Enterocytes - pathology ; Female ; Gastroenterology and Hepatology ; Gluten-free diet ; Humans ; India ; Intestinal Diseases - diagnosis ; Intestinal Diseases - pathology ; Male ; Middle Aged ; Mild enteropathy ; Mucosal apoptosis ; Tertiary Care Centers ; Villous abnormality ; Young Adult</subject><ispartof>Digestive and liver disease, 2016-11, Vol.48 (11), p.1290-1295</ispartof><rights>Editrice Gastroenterologica Italiana S.r.l.</rights><rights>2016 Editrice Gastroenterologica Italiana S.r.l.</rights><rights>Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-509c680fa390c6dbc4fab219a803a3e1ed616766c06efcc86f0359673eb5d9b23</citedby><cites>FETCH-LOGICAL-c408t-509c680fa390c6dbc4fab219a803a3e1ed616766c06efcc86f0359673eb5d9b23</cites><orcidid>0000-0002-2474-2194</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1590865816304728$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27378705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Das, Prasenjit</creatorcontrib><creatorcontrib>Gahlot, Gaurav P.S</creatorcontrib><creatorcontrib>Mehta, Ritu</creatorcontrib><creatorcontrib>Makharia, Archita</creatorcontrib><creatorcontrib>Verma, Anil K</creatorcontrib><creatorcontrib>Sreenivas, V</creatorcontrib><creatorcontrib>Panda, Subrat K</creatorcontrib><creatorcontrib>Ahuja, Vineet</creatorcontrib><creatorcontrib>Gupta, Siddhartha Datta</creatorcontrib><creatorcontrib>Makharia, Govind K</creatorcontrib><title>Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease</title><title>Digestive and liver disease</title><addtitle>Dig Liver Dis</addtitle><description>Abstract Background Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titer and mild enteropathy. Aim We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Methods Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 &amp;1) (n = 26), advanced enteropathy (Marsh grade ≥2) (n = 41) and control biopsies (n = 12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. Results End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labeling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Conclusions Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Advanced enteropathy</subject><subject>Apoptosis</subject><subject>Biomarkers - metabolism</subject><subject>Biopsy</subject><subject>Celiac disease</subject><subject>Celiac Disease - pathology</subject><subject>Cell Proliferation</subject><subject>Cross-Sectional Studies</subject><subject>Crypt regeneration</subject><subject>Duodenum - pathology</subject><subject>Enterocytes - pathology</subject><subject>Female</subject><subject>Gastroenterology and Hepatology</subject><subject>Gluten-free diet</subject><subject>Humans</subject><subject>India</subject><subject>Intestinal Diseases - diagnosis</subject><subject>Intestinal Diseases - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mild enteropathy</subject><subject>Mucosal apoptosis</subject><subject>Tertiary Care Centers</subject><subject>Villous abnormality</subject><subject>Young Adult</subject><issn>1590-8658</issn><issn>1878-3562</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-LFDEQxRtR3HX1A3iRHL30WEmmkzSCIIv_YMEF9RzSSTWTtqfTJumRPux3N8OMgntYKEglvPeo_KqqXlLYUKDizbBxo9uw0m6gFOWPqkuqpKp5I9jj0jct1Eo06qJ6ltIAwKho4Gl1wSSXSkJzWd3dmuxxyon89nlH9n50pFwxhtnk3Up25oDEzGHOIXtL_DQscSWhP4vsmjGR5IvPRJIDyTuTi4oYdzCTxf_DyrvF0RtLnE9oEj6vnvRmTPjifF5VPz5--H79ub75-unL9fub2m5B5bqB1goFveEtWOE6u-1Nx2hrFHDDkaITVEghLAjsrVWiB960QnLsGtd2jF9Vr0-5cwy_FkxZ730qo4xmwrAkTRUTkrK2lUVKT1IbQ0oRez1Hvzdx1RT0kboedKGuj9Q1lKK8eF6d45duj-6f4y_mInh7EmD55MFj1MkW6oWPj2izdsE_GP_untuOfvLWjD9xxTSEJU6FnqY6MQ3623Htx61TwWErmeJ_AJZBqgY</recordid><startdate>20161101</startdate><enddate>20161101</enddate><creator>Das, Prasenjit</creator><creator>Gahlot, Gaurav P.S</creator><creator>Mehta, Ritu</creator><creator>Makharia, Archita</creator><creator>Verma, Anil K</creator><creator>Sreenivas, V</creator><creator>Panda, Subrat K</creator><creator>Ahuja, Vineet</creator><creator>Gupta, Siddhartha Datta</creator><creator>Makharia, Govind K</creator><general>Elsevier Ltd</general><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>7X8</scope><orcidid>https://orcid.org/0000-0002-2474-2194</orcidid></search><sort><creationdate>20161101</creationdate><title>Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease</title><author>Das, Prasenjit ; Gahlot, Gaurav P.S ; Mehta, Ritu ; Makharia, Archita ; Verma, Anil K ; Sreenivas, V ; Panda, Subrat K ; Ahuja, Vineet ; Gupta, Siddhartha Datta ; Makharia, Govind K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-509c680fa390c6dbc4fab219a803a3e1ed616766c06efcc86f0359673eb5d9b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Advanced enteropathy</topic><topic>Apoptosis</topic><topic>Biomarkers - metabolism</topic><topic>Biopsy</topic><topic>Celiac disease</topic><topic>Celiac Disease - pathology</topic><topic>Cell Proliferation</topic><topic>Cross-Sectional Studies</topic><topic>Crypt regeneration</topic><topic>Duodenum - pathology</topic><topic>Enterocytes - pathology</topic><topic>Female</topic><topic>Gastroenterology and Hepatology</topic><topic>Gluten-free diet</topic><topic>Humans</topic><topic>India</topic><topic>Intestinal Diseases - diagnosis</topic><topic>Intestinal Diseases - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mild enteropathy</topic><topic>Mucosal apoptosis</topic><topic>Tertiary Care Centers</topic><topic>Villous abnormality</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Das, Prasenjit</creatorcontrib><creatorcontrib>Gahlot, Gaurav P.S</creatorcontrib><creatorcontrib>Mehta, Ritu</creatorcontrib><creatorcontrib>Makharia, Archita</creatorcontrib><creatorcontrib>Verma, Anil K</creatorcontrib><creatorcontrib>Sreenivas, V</creatorcontrib><creatorcontrib>Panda, Subrat K</creatorcontrib><creatorcontrib>Ahuja, Vineet</creatorcontrib><creatorcontrib>Gupta, Siddhartha Datta</creatorcontrib><creatorcontrib>Makharia, Govind K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive and liver disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Das, Prasenjit</au><au>Gahlot, Gaurav P.S</au><au>Mehta, Ritu</au><au>Makharia, Archita</au><au>Verma, Anil K</au><au>Sreenivas, V</au><au>Panda, Subrat K</au><au>Ahuja, Vineet</au><au>Gupta, Siddhartha Datta</au><au>Makharia, Govind K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease</atitle><jtitle>Digestive and liver disease</jtitle><addtitle>Dig Liver Dis</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>48</volume><issue>11</issue><spage>1290</spage><epage>1295</epage><pages>1290-1295</pages><issn>1590-8658</issn><eissn>1878-3562</eissn><abstract>Abstract Background Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titer and mild enteropathy. Aim We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Methods Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 &amp;1) (n = 26), advanced enteropathy (Marsh grade ≥2) (n = 41) and control biopsies (n = 12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. Results End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labeling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Conclusions Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>27378705</pmid><doi>10.1016/j.dld.2016.06.013</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-2474-2194</orcidid></addata></record>
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subjects Adolescent
Adult
Advanced enteropathy
Apoptosis
Biomarkers - metabolism
Biopsy
Celiac disease
Celiac Disease - pathology
Cell Proliferation
Cross-Sectional Studies
Crypt regeneration
Duodenum - pathology
Enterocytes - pathology
Female
Gastroenterology and Hepatology
Gluten-free diet
Humans
India
Intestinal Diseases - diagnosis
Intestinal Diseases - pathology
Male
Middle Aged
Mild enteropathy
Mucosal apoptosis
Tertiary Care Centers
Villous abnormality
Young Adult
title Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease
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