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


OBJECTIVE
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.
Verbeek
Wieke H M
WH
Department of Gastroenterology, VU University Medical Center, 1007 MB, Amsterdam, The Netherlands. whm.verbeek@vumc.nl
Goerres
Marije S
MS
von Blomberg
B Mary E
BM
Oudejans
Joost J
JJ
Scholten
Petra E T
PE
Hadithi
Muhammed
M
Al-Toma
Abdul
A
Schreurs
Marco W J
MW
Mulder
Chris J J
CJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D004386:Duodenum / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology*