title: Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease.
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.
  
  
  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.
authors.affiliation: Department of Gastroenterology, VU University Medical Center, 1007 MB, Amsterdam, The Netherlands. whm.verbeek@vumc.nl
authors.forename: Wieke H M
authors.initials: WH
authors.lastname: Verbeek
authors.forename: Marije S
authors.initials: MS
authors.lastname: Goerres
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Petra E T
authors.initials: PE
authors.lastname: Scholten
authors.forename: Muhammed
authors.initials: M
authors.lastname: Hadithi
authors.forename: Abdul
authors.initials: A
authors.lastname: Al-Toma
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
mesh_terms: 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*