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Continual monitoring of intraepithelial lymphocyte immunophenotype and clonality is more important than snapshot analysis in the surveillance of refractory coeliac disease
  1. H Liu1,
  2. R Brais1,
  3. A Lavergne-Slove2,
  4. Q Jeng3,
  5. K Payne1,
  6. H Ye3,
  7. Z Liu3,
  8. J Carreras3,
  9. Y Huang3,
  10. C M Bacon4,
  11. R A Hamoudi3,
  12. V Save1,
  13. L Venkatraman5,
  14. P G Isaacson6,
  15. J Woodward7,
  16. M-Q Du3
  1. 1Department of Histopathology, Addenbrooke's Hospital, Cambridge, UK
  2. 2Anatomie Pathologique, Hôpital Lariboisière, AP-HP, University Paris 7, France
  3. 3Department of Pathology, University of Cambridge, Cambridge, UK
  4. 4Northern Institute for Cancer Research, Newcastle University, Newcastle, UK
  5. 5Department of Histopathology, Royal Victoria Hospital, Belfast, UK
  6. 6Department of Histopathology, University College London Hospitals, London, UK
  7. 7Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK
  1. Correspondence to Professor Ming-Qing Du, Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Level 3 Lab Block, Box 231, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; mqd20{at} Dr Hongxiang Liu, Department of Histopathology, Addenbrooke's Hospital, Level 5 Lab Block, Box 235, Hills Road, Cambridge CB2 0QQ, UK; hl291{at}


Objective An aberrant immunophenotype and monoclonality of intraepithelial lymphocytes (IELs) are frequently found in refractory coeliac disease (RCD). However, the utility of continual monitoring of IEL immunophenotype and clonality in the surveillance of RCD remains to be studied.

Design The diagnostic and follow-up biopsies from 33 patients with CD, 7 with suspected RCD, 41 with RCD and 20 with enteropathy-associated T cell lymphoma (EATL) (including 11 evolved from RCD) were investigated by CD3ɛ/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged T cell receptor (TCR) genes.

Results An aberrant immunophenotype (CD3ɛ+CD8 IELs ≥40%) and monoclonality were detected occasionally in CD biopsies, either transiently in patients with CD not compliant with a gluten-free diet or in those who subsequently developed suspected RCD, RCD or EATL. In contrast, the aberrant immunophenotype and monoclonality were found in 30 of 41 (73%) and 24 of 37 (65%) biopsies, respectively, at the time of RCD diagnosis. Among the patients with RCD who did not show these abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases gained an aberrant immunophenotype and monoclonality, respectively, during follow-up. Irrespective of whether detected in diagnostic or follow-up biopsies, persistence of both abnormalities was characteristic of RCD. Importantly, the presence of concurrent persistent monoclonality and aberrant immunophenotype, especially ≥80% CD3ɛ+CD8 IELs, was a strong predictor of EATL development in patients with RCD (p=0.001).

Conclusions Continual monitoring of both immunophenotype and clonality of IELs is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.

  • Aberrant immunophenotype
  • clonality analysis
  • coeliac disease
  • follow-up
  • immunohistochemistry
  • intraepithelial T lymphocytes
  • lymphoma
  • PCR
  • refractory coeliac disease
  • T lymphocytes

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  • Funding Addenbrooke's Charitable Trust, UK; CRUK; Leukaemia Research Fund, UK; Leukemia Lymphoma Society, USA; The National Institute for Health Research Cambridge Biomedical Research Center.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Cambridgeshire 2 Research Ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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