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01.12.2012 | Original Article

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

verfasst von: Shalimar, Prasenjit Das, Vishnubhatla Sreenivas, Siddhartha Datta Gupta, Subrat K. Panda, Govind K. Makharia

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2012

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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 However, it also suppresses epithelial regeneration; hence, if used, it should be withdrawn after an initial short course.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)

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Titel: 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
verfasst von: Shalimar
Prasenjit Das
Vishnubhatla Sreenivas
Siddhartha Datta Gupta
Subrat K. Panda
Govind K. Makharia
Publikationsdatum: 01.12.2012
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2012
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-012-2294-1

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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