ORIGINAL ARTICLE

Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract

B Shen¹, E M Porter², E Reynoso², C Shen⁴, D Ghosh⁵, J T Connor⁶, J Drazba⁵, H K Rho⁵, T L Gramlich⁷, R Li⁸, A H Ormsby⁷, M-S Sy⁸, T Ganz³, C L Bevins⁵

¹ Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
² Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA
³ Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, California 90095, USA
⁴ Gastroendoscopy Unit, Qidong City Hospital, Qidong, Jiangsu Province, China 226200
⁵ The Lerner Research Institute, The Cleveland Clinic Foundation
⁶ Departments of Biostatistics and Epidemiology, The Cleveland Clinic Foundation
⁷ Department of Anatomic Pathology, The Cleveland Clinic Foundation
⁸ Department of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue Cleveland, OH 44106, USA

Correspondence to:
Correspondence to:
Dr C L Bevins
Department of Medical Microbiology and Immunology, University of California School of Medicine, One Shields Avenue, Tupper Hall, Room 3146, Davis, California 95616, USA; CLBevins{at}ucdavis.edu

Background: Upper gastrointestinal tract intestinal metaplasia (IM) is termed Barrett’s oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on its location. BO and GIM are associated with chemical exposure resulting from gastro–oesophageal reflux and chronic Helicobacter pylori infection, respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic granules, are found in a subset of IM at these sites, but histology may not accurately detect them.

Aim: To determine human defensin 5 (HD5; an antimicrobial peptide produced by PCs) expression in BO and GIM, and to investigate its association with H pylori infection.

Methods: Endoscopic biopsies from 33 patients with BO and 51 with GIM, and control tissues, were examined by routine histology and for H pylori infection and HD5 mRNA and protein expression.

Results: In normal tissues, HD5 expression was specific for PCs in the small intestine. Five patients with BE and 42 with GIM expressed HD5, but few HD5 expressing cells in IM had the characteristic histological features of PCs. Most HD5 positive specimens were H pylori infected and most HD5 negative specimens were not infected.

Conclusions: HD5 immunohistochemistry was often positive in IM when PCs were absent by conventional histology. Thus, HD5 immunohistochemistry may be superior to histology for identifying metaplastic PCs and distinguishing GIM from BO. The higher frequency of HD5 expression in GIM than in BO is associated with a higher frequency of H pylori infection, suggesting that in IM PCs may form part of the mucosal antibacterial response.

Abbreviations: aa, amino acids; BO, Barrett’s oesophagus; CI, confidence interval; EGJ, oesophagogastric junction; ELISA, enzyme linked immunosorbent assay; GERD, gastro–oesophageal reflux disease; GI, gastrointestinal; GIM, gastric intestinal metaplasia; HD5, human defensin5; H&E, haematoxylin and eosin; IM, intestinal metaplasia; OR, odds ratio; PBS, phosphate buffered saline; PCR, polymerase chain reaction; r, recombinant; RT, reverse transcription; sPLA₂, secretory phospholipase A₂; PC, Paneth cells

Keywords: Barrett’s oesophagus; intestinal metaplasia; Paneth cells; defensins; Helicobacter pylori

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