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
- 351 Downloads
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.
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.
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 However, it also suppresses epithelial regeneration; hence, if used, it should be withdrawn after an initial short course.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)
KeywordsGluten-free diet Prednisolone Immunohistochemistry Apoptotic index Cell regeneration Apoptosis
Conflict of interest
- 19.Shiner M, Eran M, Freier S, et al. Are intraepithelial lymphocytes in celiac mucosa responsible for inducing programmed cell death (apoptosis) in enterocytes? Histochemical demonstration of perforins in cytoplasmic granules of intraepithelial lymphocytes. J Pediatr Gastroenterol Nutr. 1998;27:393–396.PubMedCrossRefGoogle Scholar
- 25.Marsh MN. Mucosal pathology in gluten sensitivity. In: Marsh MN, ed. Coeliac Disease. Blackwell: Oxford; 1992:136–191.Google Scholar
- 28.Weissman G. Localization and stabilization of lysosomes. Fed Proc. 1964;23:1038–1044.Google Scholar
- 30.Das P, Shalimar, Sreenivas V, Dattagupta S, Panda SK, Makharia GK. Mechanism of villous atrophy in celiac disease: role of apoptosis and epithelial regeneration. J Gastroenterol Hepatol. 2010;25:A36 (abstract).Google Scholar
- 31.Van der Woude CJ, Jansen PLM, Tiebosch ATMG, et al. Active celiac disease induces an anti-apoptotic phenotype which limits apoptosis. 2004; http://dissertations.ub.rug.nl/FILES/faculties/medicine/2004/c.j.van.der.woude/c6.pdf. Accessed April 28, 2011.