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Front. Immunol. | doi: 10.3389/fimmu.2019.02742

Flow cytometry contributions for the diagnosis and immunopathological characterization of primary immunodeficiency diseases with immune dysregulation

  • 1Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
  • 2Department of Rheumatology and Clinical Immunology, Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Freiburg University Medical Center, Germany
  • 3Immunogenic Inc, Brazil
  • 4Department of Hematology, Oncology, and Stem-Cell Transplantation, Freiburg University Medical Center, Germany
  • 5South Australian Health and Medical Research Institute (SAHMRI), Australia
  • 6INSERM U932, SiRIC Translational Immunotherapy Team, Institut Curie, Paris Sciences et Lettres Research University, France
  • 7Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, United Arab Emirates
  • 8Department of Pediatrics, Faculty of Medicine, Federal University of Uberlandia, Brazil
  • 9Department of Pediatrics, School of Medicine, University of Washington, United States
  • 10Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Brazil

Almost 70 years after establishing the concept of primary immunodeficiency disorders (PIDs), more than 320 monogenic inborn errors of immunity have been identified thanks to the remarkable contribution of high-throughput genetic screening in the last decade. Approximately 40 of these PIDs present with autoimmune or auto-inflammatory symptoms as the primary clinical manifestation instead of infections. These PIDs are now recognized as diseases of immune dysregulation. Loss-of function mutations in genes such as FOXP3, CD25, LRBA, IL-10, IL10RA, and IL10RB, as well as heterozygous gain-of-function mutations in JAK1 and STAT3 have been reported as causative of these disorders. Identifying these syndromes has considerably contributed to expanding our knowledge on the mechanisms of immune regulation and tolerance. Although whole exome and whole genome sequencing have been extremely useful in identifying novel causative genes underlying new phenotypes, these approaches are time-consuming and expensive. Patients with monogenic syndromes associated with autoimmunity require faster diagnostic tools to delineate therapeutic strategies and avoid organ damage. Since these PIDs present with severe life-threatening phenotypes, the need for a precise diagnosis in order to initiate appropriate patient management is necessary. More traditional approaches such as flow cytometry are therefore a valid option. Here, we review the application of flow cytometry and discuss the relevance of this powerful technique in diagnosing patients with PIDs presenting with immune dysregulation. In addition, flow cytometry represents a fast, robust, and sensitive approach that efficiently uncovers new immunopathological mechanisms underlying monogenic PIDs.

Keywords: Flow Cytometry, Primary Immunodeficiency Disorder (PID), Autoimmunity, immune dysregulaiton, Mutation

Received: 02 Sep 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Cabral-Marques, Schimke, Oliveira Jr, El Khawanky, Ramos, Al-Ramadi, Segundo, Ochs and Condino-Neto. 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: PhD. Otavio Cabral-Marques, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil,