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Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: immunological determinants
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  1. R C Fitzgerald1,
  2. B A Onwuegbusi1,
  3. M Bajaj-Elliott2,
  4. I T Saeed3,
  5. W R Burnham3,
  6. M J G Farthing4
  1. 1Cancer Cell Unit, Hutchison-MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK
  2. 2Department of Adult and Paediatric Gastroenterology, St Bart's and the London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK
  3. 3Havering Hospitals NHS Trust, Romford, Essex RM3 OBE, UK
  4. 4University of Glasgow, 12 Southpark Terrace, Glasgow G12 8LG, UK
  1. Correspondence to:
    Dr R C Fitzgerald, Cancer Cell Unit, Hutchison-MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK;
    rcf{at}hutchison-mrc.cam.ac.uk

Abstract

Background and aims: Approximately 10% of adults experience gastro-oesophageal reflux symptoms with a variable oesophageal response. A total of 60% have no endoscopic abnormality, 30% have oesophagitis, and 10% have Barrett's oesophagus. We investigated whether the inflammatory cell infiltrate and cytokine profiles of these clinical phenotypes merely vary in severity or are fundamentally different.

Methods: Patients with reflux symptoms and a normal oesophagus (n=18), oesophagitis (n=26), and Barrett's oesophagus (n=22 newly diagnosed, n=28 surveillance) were recruited. Endoscopic and histopathological degrees of inflammation were scored. Cytokine expression was determined by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry.

Results: In oesophagitis, endoscopic and histopathological grades of inflammation correlated highly. mRNA expression of proinflammatory interleukin (IL)-1β, IL-8, and interferon γ (IFN-γ) were increased 3–10-fold compared with non-inflamed squamous or Barrett's oesophageal samples. There was a modest increase in anti-inflammatory IL-10 but no increase in IL-4. In Barrett's oesophagus, 29/50 had no endoscopic evidence of inflammation and histopathological inflammation was mild in 17/50 and moderate in 24/50, independent of acid suppressants. Expression of IL-1β, IL-8, and IFN-γ was similar to non-inflamed squamous mucosa. IL-10 was increased 1.6-fold similar to oesophagitis. IL-4 was increased fourfold, with 100-fold increase in IL-4/T cell receptor expression, compared with squamous oesophagus or oesophagitis.

Conclusions: Barrett's oesophagus is characterised by a distinct Th-2 predominant cytokine profile compared with the proinflammatory nature of oesophagitis. The specific oesophageal immune responses may influence disease development and progression.

  • Barrett's oesophagus
  • oesophagitis
  • gastro-oesophageal reflux disease
  • inflammation
  • cytokines
  • GORD, gastro-oesophageal reflux disease
  • TCR, T cell receptor
  • PPI, proton pump inhibitor
  • RT-PCR, reverse transcriptase-polymerase chain reaction
  • IFN-γ, interferon γ
  • IL, interleukin
  • PPI, proton pump inhibitor
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