Original Article

Digestive Diseases and Sciences

, Volume 57, Issue 12, pp 3116-3125

Effect of Addition of Short Course of Prednisolone to Gluten-Free Diet on Mucosal Epithelial Cell Regeneration and Apoptosis in Celiac Disease: A Pilot Randomized Controlled Trial

  • ShalimarAffiliated withDepartment of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences
  • , Prasenjit DasAffiliated withDepartment of Pathology, All India Institute of Medical Sciences
  • , Vishnubhatla SreenivasAffiliated withDepartment of Biostatistics, All India Institute of Medical Sciences
  • , Siddhartha Datta GuptaAffiliated withDepartment of Pathology, All India Institute of Medical Sciences
  • , Subrat K. PandaAffiliated withDepartment of Pathology, All India Institute of Medical Sciences
  • , Govind K. MakhariaAffiliated withDepartment of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences Email author 

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Abstract

Background

Identification of adjuvant treatment is necessary for rapid and effective treatment in patients with celiac disease. In a pilot randomized controlled trial, the effect of prednisolone on enterocyte apoptosis and regeneration in celiac disease was investigated.

Patients and Methods

Thirty-three treatment-naïve patients with celiac disease were randomized to either gluten-free diet (GFD, n = 17) or GFD + prednisolone (1 mg/kg for 4 weeks, n = 16). Duodenal biopsies were taken at baseline and at 4 and 8 weeks posttreatment. Six patients with functional dyspepsia were recruited as controls. All these biopsies were stained for markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common apoptotic pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic (AI) and proliferation indices (PI) were compared.

Results

At baseline duodenal biopsies, the end apoptotic products H2AX and M30 were significantly increased. In comparison with those treated with GFD alone, after 4 weeks of GFD + prednisolone treatment, some markers of both intrinsic and common apoptotic pathways showed rapid decline. After prednisolone withdrawal, there was overexpression of H2AX, CC3, and p53 in the latter group. In comparison with those treated with only GFD, patients treated with prednisolone showed suppression of mucosal PI, which started rising again after withdrawal of prednisolone.

Conclusions

Apoptosis takes place in mucosal epithelium in celiac disease. Addition of short course of prednisolone suppresses apoptosis rapidly. However, it also suppresses epithelial regeneration; hence, if used, it should be withdrawn after an initial short course. (Registered at clinicaltrials.gov; NCT01045837)

Keywords

Gluten-free diet Prednisolone Immunohistochemistry Apoptotic index Cell regeneration Apoptosis