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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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 &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. Published by Elsevier Ltd. 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 &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 &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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