Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease

Clin Immunol. 2008 Jan;126(1):48-56. doi: 10.1016/j.clim.2007.09.002. Epub 2007 Nov 26.


Background: Refractory celiac disease (RCD) patients with aberrant, often clonal, intraepithelial T-cells are at high risk for development of enteropathy associated T-cell lymphoma (EATL). Early detection of those patients that actually develop EATL is of utmost importance for curative intervention.

Aim: First, to establish an optimal cut-off value for the percentage of aberrant lymphocytes, previously determined based on clinical observations, via reference ranges for aberrant T-cells in the duodenal mucosa of celiac disease patient and control groups. Secondly, to compare aberrancy with intestinal T-cell clonality as a prognostic parameter for EATL development in RCD.

Methods: Immunophenotyping using flow cytometry was performed on small intestinal biopsy-derived lymphocytes, obtained from distinct celiac disease (CD) patient and control groups (N=167 in total). T-cell clonality in duodenal biopsy specimens was assessed by PCR in RCD, ulcerative jejunitis and EATL patients (N=31 in total).

Results: In 95% of non-refractory CD patients, the highest percentage aberrant T-cells was 20%. Using this cut-off value, EATL development was exclusively seen in RCD with more than 20% aberrant T-cells (median 52% aberrant T-cells, range 27-94%). When compared with T-cell clonality analysis, >20% aberrancy showed a much higher negative predictive value and sensitivity (both 100%) for EATL development in RCD patients than T-cell clonality analysis (respectively 75% and 78%).

Conclusions: Quantification of aberrant T-cells by flow cytometry is preferable to T-cell clonality analysis for identification of RCD patients at risk for EATL development. A cut-off value of 20% is of use in risk stratification, therapeutic options and subsequent follow-up of RCD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Celiac Disease / complications*
  • Celiac Disease / immunology*
  • Celiac Disease / pathology
  • Duodenum / immunology*
  • Duodenum / pathology
  • Female
  • Flow Cytometry*
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor*
  • Humans
  • Immunophenotyping
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Lymphoma, T-Cell / diagnosis*
  • Lymphoma, T-Cell / etiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • T-Lymphocytes / immunology*