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Front. Physiol. | doi: 10.3389/fphys.2018.01877

TREC and KREC levels as a predictors of lymphocyte subpopulations measured by flow cytometry

 Ilya Korsunskiy1, 2, 3*,  Oleg Blyuss4,  Maria Gordukova1,  Nataliia V. Davydova1,  Susan Y. Gordleeva5, Robert Molchanov6, Alan Asmanov7, Dmitrii Peshko2, Natalia Zinovieva1, Sergey Zimin1, Vladimir Lazarev2, Aminat Salpagarova2,  Maxim L. Filipenko8, Ivan Kozlov3, Andrey Prodeus1, 3, Anatoliy Korsunskiy1, 2, Peter Hsu9, 10 and  Daniel Munblit2, 10, 11*
  • 1Speransky Children Hospital No.9, Russia
  • 2I.M. Sechenov First Moscow State Medical University, Russia
  • 3Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Russia
  • 4Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
  • 5N. I. Lobachevsky State University of Nizhny Novgorod, Russia
  • 6State Institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine", Ukraine
  • 7Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Russia
  • 8Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (RAS), Russia
  • 9Kids Research Institute, The Children’s Hospital at Westmead, Australia
  • 10Worldwide Universities Network (WUN), United States
  • 11Imperial College London, United Kingdom

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases or malignancies. Early detection of other PID remains a challenge. Particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice.

This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins.

We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8 and CD19), IgA, IgM and IgG analysis.

A total of 839 samples were analysed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70 – 0.76) for CD3, 0.74 (95% CI 0.71 – 0.77) for CD4 and 0.67 (95% CI 0.63 – 0.70) for CD8 respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69 – 0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r=0.55, p<0.01) and KREC with CD19 (r=0.56, p<0.01).

In this study, a promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis.

Keywords: TREC, KREC, PID, Primary immune deficiencies, Flow Cytometry, lymphocyte subpopulations, CD3, CD4, CD8, CD19, Immunoglobilins

Received: 29 Sep 2018; Accepted: 11 Dec 2018.

Edited by:

Shangbin Chen, Huazhong University of Science and Technology, China

Reviewed by:

Maria Giulia Bacalini, University of Bologna, Italy
Igor V. Kudryavtsev, Institute of Experimental Medicine (RAS), Russia  

Copyright: © 2018 Korsunskiy, Blyuss, Gordukova, Davydova, Gordleeva, Molchanov, Asmanov, Peshko, Zinovieva, Zimin, Lazarev, Salpagarova, Filipenko, Kozlov, Prodeus, Korsunskiy, Hsu and Munblit. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Ilya Korsunskiy, Speransky Children Hospital No.9, Moscow, 123317, Moscow Oblast, Russia,
Dr. Daniel Munblit, I.M. Sechenov First Moscow State Medical University, Moscow, Russia,