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      Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification

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          Abstract

          Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. We herein report the 2019 phenotypic classification, including the 65 new conditions. The diagnostic algorithms are based on clinical and laboratory phenotypes for each of the ten broad categories of IEI.

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          Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

          We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.
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            Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience.

            The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries.
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              The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies

              Since the 1990s, the International Union of Immunological Societies (IUIS) PID expert committee (EC), now called Inborn Errors of Immunity Committee, has published every other year a classification of the inborn errors of immunity. This complete catalog serves as a reference for immunologists and researchers worldwide. However, it was unadapted for clinicians at the bedside. For those, the IUIS PID EC is now publishing a phenotypical classification since 2013, which proved to be more user-friendly. There are now 320 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. We herein propose the revised 2017 phenotypic classification, based on the accompanying 2017 IUIS Inborn Errors of Immunity Committee classification.
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                Author and article information

                Contributors
                profbousfiha@gmail.com
                Journal
                J Clin Immunol
                J. Clin. Immunol
                Journal of Clinical Immunology
                Springer US (New York )
                0271-9142
                1573-2592
                11 February 2020
                11 February 2020
                2020
                : 40
                : 1
                : 66-81
                Affiliations
                [1 ]GRID grid.412148.a, ISNI 0000 0001 2180 2473, Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergy LICIA, Faculty of Medecine and Pharmacy, , King Hassan II University, ; Casablanca, Morocco
                [2 ]GRID grid.414346.0, ISNI 0000 0004 0647 7037, Clinical Immunology Unit, Pediatric Infectiouse Disease Departmentn Children’s Hospital, , Ibn Rochd University Hospital, ; Casablanca, Morocco
                [3 ]GRID grid.501381.e, Laboratoire national de référence, , University Mohamed VI of Health Sciences, ; Casablanca, Morocco
                [4 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, APHP, , Paris University, ; Paris, France
                [5 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR1163, Imagine Institute, Necker Hospital for Sick Children, , Paris University, ; Paris, France
                [6 ]GRID grid.411196.a, ISNI 0000 0001 1240 3921, Department of Pediatrics, Faculty of Medicine, , Kuwait University, ; Kuwait City, Kuwait
                [7 ]GRID grid.2515.3, ISNI 0000 0004 0378 8438, Division of Immunology, Children’s Hospital Boston, ; Boston, USA
                [8 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, ; New York, USA
                [9 ]Ruth’s Children’s Hospital-Technion, Haifa, Israel
                [10 ]GRID grid.412881.6, ISNI 0000 0000 8882 5269, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, , Universidad de Antioquia UdeA, ; Medellin, Colombia
                [11 ]GRID grid.419681.3, ISNI 0000 0001 2164 9667, Laboratory of Clinical Immunology & Microbiology, , National Institute of Allergy and Infectious Diseases, National Institutes of Health, ; Bethesda, USA
                [12 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Dr von Hauner Children’s Hospital, , Ludwig-Maximilians-University Munich, ; Munich, Germany
                [13 ]GRID grid.265073.5, ISNI 0000 0001 1014 9130, Department of Pediatrics and Developmental Biology, , Tokyo Medical and Dental University (TMDU), ; Tokyo, Japan
                [14 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Pediatrics, , University of Washington and Seattle Children’s Research Institute, ; Seattle, USA
                [15 ]GRID grid.7452.4, ISNI 0000 0001 2217 0017, Department of Clinical Immunology, Hôpital Saint-Louis, APHP, , University Paris Diderot, ; Sorbonne Paris, Cité, Paris, France
                [16 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Pediatrics, , University of California San Francisco and UCSF Benioff Children’s Hospital, ; San Francisco, USA
                [17 ]GRID grid.134907.8, ISNI 0000 0001 2166 1519, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, , The Rockefeller University, ; New York, USA
                [18 ]GRID grid.413575.1, ISNI 0000 0001 2167 1581, Howard Hughes Medical Institute, ; New York, USA
                [19 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institute, Necker Hospital for Sick Children, , Paris University, ; Paris, France
                [20 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Pediatric Hematology-Immunology Unit, , Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (APHP), ; Paris, France
                [21 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Division of Allergy Immunology, Department of Pediatrics, The Children’s Hospital of Philadelphia, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, USA
                [22 ]GRID grid.415306.5, ISNI 0000 0000 9983 6924, Garvan Institute of Medical Research, ; Darlinghurst, Australia
                [23 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, St Vincent’s Clinical School, Faculty of Medicine, UNSW, ; Sydney, Australia
                Article
                758
                10.1007/s10875-020-00758-x
                7082388
                32048120
                4c704974-c8b1-41ed-9d4f-477b0aea51d3
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 December 2019
                : 22 January 2020
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Immunology
                iuis,primary immune deficiency,inborn errors of immunity,immune dysregulation,autoinflammatory disorders,classification

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