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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.
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http://dx.doi.org/10.1016/j.molimm.2012.01.014 | DOI Listing |
Int J Mol Sci
September 2024
Gastroenterology Department, Hospital de Vila Franca de Xira, 2600-009 Lisbon, Portugal.
Clin Gastroenterol Hepatol
November 2024
Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands. Electronic address:
Refractory celiac disease type 2 (RCDII) is a rare condition with high mortality because of a lack of effective treatment strategies. RCDII is caused by clonal expansion of intraepithelial lymphocytes (IELs). Gain-of-function JAK1 mutations are frequently found in these cells.
View Article and Find Full Text PDFDiagnostics (Basel)
August 2023
Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland.
EATL is an aggressive T-cell non-Hodgkin lymphoma with poor prognosis and is largely localized to the small intestine. EATL is closely associated with coeliac disease (CD) and is seen mostly in patients originating from Northern Europe. Various factors are associated with an increased risk of developing EATL, such as viral infection, advanced age, being male, and the presence of the HLA-DQ2 haplotype.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
June 2022
Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:
Background & Aims: Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3surfaceCD3CD7CD56 aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII.
View Article and Find Full Text PDFDig Dis
November 2020
Department of Immunology, Hospital Universitario Ramón y Cajal, Madrid, Spain,
Background: Refractory celiac disease type II (RCD-II) is a very rare yet severe complication of celiac disease (CD) with a 50% rate of progression to Enteropathy-associated T-cell lymphoma (EATL). Timely diagnosis and treatment of RCD-II is of the essence and requires the identification of a population of frequently clonal, phenotypically aberrant intraepithelial lymphocytes (IELs). Flow Cytometry of intestinal IELs is the recommended method to identify the aberrant surface CD3-negative (sCD3-) intracytoplasmic CD3-positive (icCD3ε+) IELs, and a proportion of >20% is diagnostic of RCD-II.
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