Article Text

PDF
Clonal T cell receptor gene rearrangements in coeliac disease: implications for diagnosing refractory coeliac disease
  1. Shafinaz Hussein1,
  2. Tatyana Gindin1,
  3. Stephen M Lagana1,
  4. Carolina Arguelles-Grande2,
  5. Suneeta Krishnareddy2,
  6. Bachir Alobeid1,
  7. Suzanne K Lewis2,
  8. Mahesh M Mansukhani1,
  9. Peter H R Green2,
  10. Govind Bhagat1,2
  1. 1Department of Pathology and Cell Biology, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA
  2. 2Department of Medicine, Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA
  1. Correspondence to Dr Govind Bhagat, Department of Pathology and Cell Biology, New York-Presbyterian Hospital, New York 10032, USA; gb96{at}cumc.columbia.edu

Abstract

Aims Refractory coeliac disease type II (RCDII), a rare complication of coeliac disease (CD) associated with high morbidity, requires identification of a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs) for diagnosis. However, data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII are limited.

Methods We analysed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active CD, 172 CD on gluten-free diet (GFD), 33 RCDI, and three RCDII patients and 14 patients without CD. TCR-GR patterns were divided into clonal, polyclonal and prominent clonal peaks (PCPs) and these patterns were correlated with clinical and pathological features.

Results Clonal TCR-GR products were detected in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with GFD. PCPs were observed in all disease phases (range 12%–33%). There was no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). A higher frequency of surface CD3(−) IELs was noted in cases with clonal TCR-GR, but the PCP pattern did not show associations with any clinical or pathological feature. Persistence of clonal or PCP pattern on repeat biopsy was seen for up to 2 years without evidence of RCDII.

Conclusions Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.

  • coeliac disease
  • flow cytometry
  • molecular diagnostics

Statistics from Altmetric.com

Footnotes

  • SH and TG contributed equally.

  • Handling editor Runjan Chetty.

  • Contributors PHG and GB were responsible for the study concept and design. SH, TG, CAG, MM, PHG and GB were responsbile for the acquisition of data. TG, SH and GB were involved in the analysis and interpretation of data and drafting the manuscript. TG and SH did the statistical analysis. All the authors contributed to the critical revision of the manuscript for important intellectual content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Institutional Review Board of Columbia University, New York, USA.

  • Provenance and peer review Not commissioned; externally peer reviewed.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.