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TCR Clonality Improves Diagnostic Yield of TCR Clonality in Refractory Celiac Disease

Perfetti, Vittorio MD*,†; Brunetti, Laura MD*; Biagi, Federico MD*; Ciccocioppo, Rachele MD*; Bianchi, Paola I. MD*; Corazza, Gino R. MD*

Journal of Clinical Gastroenterology: September 2012 - Volume 46 - Issue 8 - p 675–679
doi: 10.1097/MCG.0b013e31823eff20
ALIMENTARY TRACT: Original Articles

Background: Refractory celiac disease (RCD) is a preneoplastic condition as many patients develop an enteropathy-type T-cell lymphoma, a mature T-cell receptor α-β lymphoma arising in the gut with an ominous outcome. Recently, research focused on a population of intraepithelial intestinal lymphocytes expressing the same lymphoma T-cell receptor variable region (V)γ, as shown by polymerase chain reaction (PCR) analysis and sequencing. Meanwhile, the Biomedicine and Health-2 Concerted Action has made available standardized, highly specific, and sensitive PCR assays not only for but also for .

Goals: We verified whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method.

Study: Duodenal biopsies were analyzed from 15 RCD patients, 21 negative controls, and 2 positive controls (enteropathy-type T-cell lymphoma complicating celiac disease). Multiplex clonality analyses were performed according to the Biomedicine and Health-2 protocols. PCR products were cloned and sequenced.

Results: Monoclonal rearrangements were found in 5/15 samples from patients with RCD (both rearrangements in 2 cases, only in 2, and only 1 solitary Vγ clonality). Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results.

Conclusions: The combined analysis of both rearrangements allowed recognition of monoclonal populations in otherwise negative patients, with detection rates from 20% ( only) to 33% ( and ), thus raising the likelihood of early identification of RCD patients at high risk of death.

*Coeliac Centre/First Department of Internal Medicine

Department of Medical Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

This project was supported by a grant from Fondazione Celiachia “Studio di possibili fattori ambientali e sviluppo di nuove strategie terapeutiche nelle complicanze della malattia celiaca.”

The authors declare that they have nothing to disclose.

Reprints: Federico Biagi, MD, Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, P.le Golgi, 19, I-27100 Pavia, Italy (e-mail: f.biagi@smatteo.pv.it).

Received August 7, 2011

Accepted October 26, 2011

© 2012 Lippincott Williams & Wilkins, Inc.