title: 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 titre and mild enteropathy.
  
  
  OBJECTIVE
  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 and 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 labelling 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.
authors.affiliation: Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.affiliation: Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Gaurav P S
authors.initials: GP
authors.lastname: Gahlot
authors.affiliation: Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India; Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Archita
authors.initials: A
authors.lastname: Makharia
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Department of Biostatistics, India.
authors.forename: Vishnubhatla
authors.initials: V
authors.lastname: Sreenivas
authors.affiliation: Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Subrat K
authors.initials: SK
authors.lastname: Panda
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Vineet
authors.initials: V
authors.lastname: Ahuja
authors.affiliation: Department of Pathology and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Siddhartha Datta
authors.initials: SD
authors.lastname: Gupta
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India. Electronic address: govindmakharia@gmail.com.
authors.forename: Govind K
authors.initials: GK
authors.lastname: Makharia
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002446:Celiac Disease / Q000473:pathology*; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D004386:Duodenum / Q000473:pathology*; D020895:Enterocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D007194:India; D007410:Intestinal Diseases / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Advanced enteropathy; Celiac disease; Crypt regeneration; Gluten-free diet; Mild enteropathy; Mucosal apoptosis; Villous abnormality