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High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges

Anton W. Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J. M. van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A. Macintyre, Michael Hummel, Christiane Pott, Patricia J. T. A. Groenen, Kostas Stamatopoulos and the EuroClonality-NGS Consortium
J Immunol April 17, 2017, 1602050; DOI: https://doi.org/10.4049/jimmunol.1602050
Anton W. Langerak
Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands;
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Monika Brüggemann
Second Medical Department, University Hospital Schleswig-Holstein, 24105 Kiel, Germany;
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Frédéric Davi
Département d'Hématologie, Assistance Publique – Hôpitaux de Paris Hopital Pitié-Salpêtrière and Université Pierre et Marie Curie – Université Paris IV, 75005 Paris, France;
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Nikos Darzentas
Molecular Medicine Program, Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic;
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Jacques J. M. van Dongen
Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands;
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David Gonzalez
Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, United Kingdom;
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Gianni Cazzaniga
Centro Ricerca Tettamanti, Clinica Pediatrica Università Milano-Bicocca, 20900 Monza, Italy;
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Véronique Giudicelli
UMR 9002 CNRS – Université de Montpellier, 34396 Montpellier, France;
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Marie-Paule Lefranc
UMR 9002 CNRS – Université de Montpellier, 34396 Montpellier, France;
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Mathieu Giraud
Centre de Recherche en Informatique Signal et Automatique de Lille, CNRS, Université de Lille, 59000 Lille, France;
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Elizabeth A. Macintyre
Département d'Hématologie, Assistance Publique – Hôpitaux de Paris Necker-Enfants Malades and Paris Descartes, 75015 Paris, France;
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Michael Hummel
Institut für Pathologie, Charité – Universitätsmedizin Berlin, D-10117 Berlin, Germany;
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Christiane Pott
Second Medical Department, University Hospital Schleswig-Holstein, 24105 Kiel, Germany;
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Patricia J. T. A. Groenen
Department of Pathology, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, the Netherlands; and
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Kostas Stamatopoulos
Institute of Applied Biosciences, Center for Research and Technology Hellas, GR-57001 Thessaloniki, Greece
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Abstract

Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis. This concerns the preanalytical (sample preparation, target choice), analytical (amplification, NGS), and postanalytical (immunoinformatics) phases. Here we critically discuss pitfalls and challenges of IG/TR NGS methodology and its applications in hemato-oncology and immunology.

Footnotes

  • ↵1 All listed authors are members of the EuroClonality-NGS Consortium and have written this article on behalf of the entire consortium.

  • See related articles in this issue: IJspeert et al. (J. Immunol. 198, 4156; DOI: https://doi.org/10.4049/jimmunol.1601921) and Boyer et al. (J. Immunol. 198, 4148; DOI: https://doi.org/10.4049/jimmunol.1601924).

  • This work was supported by EuroClonality.

  • Received December 15, 2016.
  • Accepted January 9, 2017.
  • Copyright © 2017 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 200 (8)
The Journal of Immunology
Vol. 200, Issue 8
15 Apr 2018
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High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges
Anton W. Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J. M. van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A. Macintyre, Michael Hummel, Christiane Pott, Patricia J. T. A. Groenen, Kostas Stamatopoulos, the EuroClonality-NGS Consortium
The Journal of Immunology April 17, 2017, 1602050; DOI: 10.4049/jimmunol.1602050

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High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges
Anton W. Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J. M. van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A. Macintyre, Michael Hummel, Christiane Pott, Patricia J. T. A. Groenen, Kostas Stamatopoulos, the EuroClonality-NGS Consortium
The Journal of Immunology April 17, 2017, 1602050; DOI: 10.4049/jimmunol.1602050
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Print ISSN 0022-1767        Online ISSN 1550-6606