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Origin and immunophenotype of aberrant IEL in RCDII patients
Greetje J Tack1, Roy L J van Wanrooij, Anton W Langerak
1Gastroenterology and Hepatology, VU University Medical Center, The Netherlands. g.tack@vumc.nl
Insights
Aberrant intra-epithelial lymphocytes in refractory celiac disease type II originate from immature T cells with cytotoxic potential. Their maturity level correlates with the development of enteropathy-associated T cell lymphoma.
Area of Science:
- Gastroenterology
- Immunology
- Oncology
Background:
- Aberrant intra-epithelial lymphocytes (IELs) are key indicators of refractory celiac disease type II (RCDII).
- These cells are considered premalignant and can evolve into enteropathy-associated T cell lymphoma (EATL).
Purpose of the Study:
- To investigate the origin and characteristics of aberrant IELs in RCDII.
- To analyze T-cell receptor (TCR) rearrangements and immunophenotype of aberrant IELs.
Main Methods:
- Analysis of TCR delta, gamma, and beta rearrangements in duodenal biopsies from 18 RCDII patients and 3 RCDII cell lines.
- Phenotypic analysis of IELs isolated from RCDII patient biopsies.
Main Results:
- Aberrant IELs exhibit upregulated granzyme B and downregulated PCNA expression.
- TCR rearrangements in aberrant IELs were heterogeneous, suggesting varying maturity levels.
- RCDII cell lines also showed heterogeneous TCR rearrangement patterns.
Conclusions:
- Aberrant IELs arise from immature T lymphocytes with a cytotoxic differentiation.
- Maturity stages of aberrant IELs varied among RCDII patients.
- EATL development was observed only in patients with the most mature aberrant IEL populations.
Objectives:
Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs.
Design:
Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs isolated from biopsies derived from RCDII patients were phenotypically analysed.
Results:
Aberrant IELs showed an upregulated expression of granzyme B and decreased expression of PCNA. TCR rearrangements in the aberrant IEL population in biopsies of RCDII patients were heterogenic, which is most likely due to a variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR rearrangement pattern.
Conclusion:
Aberrant IELs originate from deranged immature T lymphocytes and display clear differentiation to a cytotoxic phenotype. Aberrant IELs displayed different stages of maturity between RCDII patients, of which only the patients harbouring the most mature aberrant IEL population developed an EATL.
