{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:55:33Z","timestamp":1787601333875,"version":"build-2736575974"},"reference-count":58,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9]]},"abstract":"\n Context<\/jats:italic>\n .\u2014The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease.\n <\/jats:p>\n \n Objectives<\/jats:italic>\n .\u2014To determine the role of apoptosis and epithelial cell regeneration in celiac disease.\n <\/jats:p>\n \n Design<\/jats:italic>\n .\u2014Twenty-five treatment-na\u00efve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated.\n <\/jats:p>\n \n Results<\/jats:italic>\n .\u2014Expression of end-apoptotic products, that is, H2AX in the cell nuclei (\n P<\/jats:italic>\n = .01) and M30 in the cell cytoplasm (\n P<\/jats:italic>\n < .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase-3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls.\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n .\u2014Treatment-na\u00efve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment-na\u00efve celiac disease imparts an additional pro-apoptotic effect.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0354-oa","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T16:18:18Z","timestamp":1377879498000},"page":"1262-1269","source":"Crossref","is-referenced-by-count":48,"title":["Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration"],"prefix":"10.5858","volume":"137","author":[{"given":"DM","family":"Shalimar","sequence":"first","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Das","sequence":"additional","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnubhatla","family":"Sreenivas","sequence":"additional","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha Datta","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subrat K.","family":"Panda","sequence":"additional","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govind K.","family":"Makharia","sequence":"additional","affiliation":[{"name":"From the Departments of Gastroenterology and Human Nutrition (Drs Shalimar and Makharia), Pathology (Drs Das, Gupta, and Panda), and Biostatistics (Dr Sreenivas), the All India Institute of Medical Sciences, New Delhi, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"issue":"8","key":"i1543-2165-137-9-1262-b01","series-title":"Arch Dis Child","first-page":"909","article-title":"Revised criteria for diagnosis of coeliac disease","volume":"65","author":"Walker-Smith\n JA,","year":"1990","unstructured":"Walker-Smith\n JA, \n \n Guandalini\n S, \n \n Schmitz\n J, \n \n Shmerling\n DH, \n \n Visakorpi\n JK. \n \n Revised criteria for diagnosis of coeliac disease. Arch Dis Child. 1990;65(8):909\u2013911."},{"issue":"6","key":"i1543-2165-137-9-1262-b02","series-title":"Gastroenterology","first-page":"1526","article-title":"AGA technical review on coeliac sprue: American Gastroenterological Association","volume":"120","author":"Ciclitira\n PJ,","year":"2001","unstructured":"Ciclitira\n PJ, \n \n King\n AL, \n \n Fraser\n JS. \n \n AGA technical review on coeliac sprue: American Gastroenterological Association. Gastroenterology. 2001;120(6):1526\u20131540."},{"issue":"1","key":"i1543-2165-137-9-1262-b03","series-title":"NIH Consens State Sci Statements","first-page":"1","article-title":"NIH consensus statement on coeliac disease","volume":"21","year":"2004","unstructured":"NIH consensus statement on coeliac disease. 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Int Immunol. 2005;17(5):513\u2013522."},{"issue":"1","key":"i1543-2165-137-9-1262-b13","series-title":"Clin Exp Immunol","first-page":"88","article-title":"Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease","volume":"128","author":"Ciccocioppo\n R,","year":"2002","unstructured":"Ciccocioppo\n R, \n \n D'al\u00f2\n S, \n \n Sabatino\n AD, \n et al\n . Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease. Clin Exp Immunol. 2002;128(1):88\u201393."},{"issue":"3","key":"i1543-2165-137-9-1262-b14","series-title":"Gut","first-page":"418","article-title":"FAS engagement drives apoptosis of enterocytes of coeliac patients","volume":"48","author":"Maiuri\n L,","year":"2001","unstructured":"Maiuri\n L, \n \n Ciacci\n C, \n \n Raia\n V, \n et al\n . FAS engagement drives apoptosis of enterocytes of coeliac patients. 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