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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.CI

Abstract

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.

Authors+Show Affiliations

Department of Gastroenterology, VU University Medical Center, 1007 MB, Amsterdam, The Netherlands. whm.verbeek@vumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18024205

Citation

Verbeek, Wieke H M., et al. "Flow Cytometric Determination of Aberrant Intra-epithelial Lymphocytes Predicts T-cell Lymphoma Development More Accurately Than T-cell Clonality Analysis in Refractory Celiac Disease." Clinical Immunology (Orlando, Fla.), vol. 126, no. 1, 2008, pp. 48-56.
Verbeek WH, Goerres MS, von Blomberg BM, et al. 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;126(1):48-56.
Verbeek, W. H., Goerres, M. S., von Blomberg, B. M., Oudejans, J. J., Scholten, P. E., Hadithi, M., Al-Toma, A., Schreurs, M. W., & Mulder, C. J. (2008). Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clinical Immunology (Orlando, Fla.), 126(1), 48-56.
Verbeek WH, et al. 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;126(1):48-56. PubMed PMID: 18024205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. AU - Verbeek,Wieke H M, AU - Goerres,Marije S, AU - von Blomberg,B Mary E, AU - Oudejans,Joost J, AU - Scholten,Petra E T, AU - Hadithi,Muhammed, AU - Al-Toma,Abdul, AU - Schreurs,Marco W J, AU - Mulder,Chris J J, Y1 - 2007/11/26/ PY - 2007/05/30/received PY - 2007/08/29/revised PY - 2007/09/17/accepted PY - 2007/11/21/pubmed PY - 2008/2/26/medline PY - 2007/11/21/entrez SP - 48 EP - 56 JF - Clinical immunology (Orlando, Fla.) JO - Clin Immunol VL - 126 IS - 1 N2 - 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. SN - 1521-6616 UR - https://www.unboundmedicine.com/medline/citation/18024205/Flow_cytometric_determination_of_aberrant_intra_epithelial_lymphocytes_predicts_T_cell_lymphoma_development_more_accurately_than_T_cell_clonality_analysis_in_Refractory_Celiac_Disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(07)01354-X DB - PRIME DP - Unbound Medicine ER -