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Optimal Strategies to Identify Aberrant Intra-Epithelial Lymphocytes in Refractory Coeliac Disease

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Abstract

Introduction

Different strategies have been developed to identify those refractory celiac disease (RCD) patients who are at risk to develop an enteropathy associated T-cell lymphoma (EATL). Flow cytometric analysis of intra-epithelial lymphocytes (IEL) with an aberrant phenotype is considered the golden standard but is not widely available. Immunohistochemistry (IHC) and T-cell receptor (TCR) rearrangement studies are commonly available but may lack sensitivity and specificity. Here, we compared the three different methods in the workup of patients suspected for RCD.

Methods

Duodenal biopsies from control patient (n = 5), RCD patients with moderately increased aberrant IEL populations (20–50 %: n = 14), and RCD patients with high numbers of aberrant IEL (>50 %: n = 5) as determined by flow cytometry were analysed by IHC and TCR-γ chain rearrangement analysis. Three pathologists scored the slides independently.

Results

Sensitivity of IHC and TCR-γ rearrangement analysis in RCD patients with high numbers of aberrant IELs was 100 and 71 %, respectively. RCD patients with aberrant cells between 25 and 50 % however, were missed by IHC and TCR in 50 and 57 % of cases, respectively. In addition, inter-rater reliability analysis of the IHC scoring revealed coder-pair Kappa coefficients between 0.28 and 0.85.

Conclusion

Immunohistochemistry and to a lesser extent TCR-γ clonality analysis are sensitive in identifying patients with high numbers of aberrant IEL populations, yet miss half of RCD patients with moderately increased numbers. In addition, IHC has a high inter-observer variability. Therefore, patients suspected for RCD should undergo flow cytometric analysis of the duodenum.

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Authorship Contributions

RLJVW designed and conducted the study, performed laboratory studies and wrote the manuscript. DMJM performed laboratory studies.

EANB, JM and LGK evaluated histological slides.

HJB and BMEVB performed and evaluated flow cytometric data.

DAMH performed and evaluated clonality analysis.

GB and CJJM designed and supervised the study, and wrote the manuscript.

Funding

This work was supported by the Coeliac Disease Consortium, The Netherlands.

Competing Interest

None of the authors states a conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    R. L. J. van Wanrooij, D. M. J. Müller, G. Bouma & C. J. J. Mulder

  2. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    E. A. Neefjes-Borst, L. G. Koudstaal, D. A. M. Heideman, H. J. Bontkes & B. M. E. von Blomberg

  3. Division of Pathology, Rijnstate Hospital, Arnhem, The Netherlands

    J. Meijer

Authors
  1. R. L. J. van Wanrooij
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  2. D. M. J. Müller
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  3. E. A. Neefjes-Borst
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  4. J. Meijer
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  5. L. G. Koudstaal
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  6. D. A. M. Heideman
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  7. H. J. Bontkes
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  8. B. M. E. von Blomberg
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  9. G. Bouma
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  10. C. J. J. Mulder
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Corresponding author

Correspondence to R. L. J. van Wanrooij.

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van Wanrooij, R.L.J., Müller, D.M.J., Neefjes-Borst, E.A. et al. Optimal Strategies to Identify Aberrant Intra-Epithelial Lymphocytes in Refractory Coeliac Disease. J Clin Immunol 34, 828–835 (2014). https://doi.org/10.1007/s10875-014-0075-7

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  • DOI: https://doi.org/10.1007/s10875-014-0075-7

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