77
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references83

          • Record: found
          • Abstract: found
          • Article: not found

          Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

          Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            BiallelicRIPK1mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation

            Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. Here, we report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired MAPK activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Type I interferon-mediated autoinflammation due to DNase II deficiency

              Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans.
                Bookmark

                Author and article information

                Contributors
                s.tangye@garvan.org.au
                Journal
                J Clin Immunol
                J. Clin. Immunol
                Journal of Clinical Immunology
                Springer US (New York )
                0271-9142
                1573-2592
                17 January 2020
                17 January 2020
                2020
                : 40
                : 1
                : 24-64
                Affiliations
                [1 ]GRID grid.415306.5, ISNI 0000 0000 9983 6924, Garvan Institute of Medical Research, ; Darlinghurst, Sydney, NSW 2010 Australia
                [2 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, Faculty of Medicine, , St Vincent’s Clinical School, UNSW, ; Sydney, NSW Australia
                [3 ]GRID grid.411196.a, ISNI 0000 0001 1240 3921, Department of Pediatrics, Faculty of Medicine, , Kuwait University, ; Kuwait City, Kuwait
                [4 ]GRID grid.414346.0, ISNI 0000 0004 0647 7037, King Hassan II University, Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergy LICIA at Faculty of Medicine and Pharmacy, Clinical Immunology Unit, Pediatric Infectiouse Disease Department, Children’s Hospital, Ibn Rochd University Hospital, ; Casablanca, Morocco
                [5 ]GRID grid.2515.3, ISNI 0000 0004 0378 8438, Division of Immunology, , Children’s Hospital Boston, ; Boston, MA USA
                [6 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Departments of Medicine and Pediatrics, , Mount Sinai School of Medicine, ; New York, NY USA
                [7 ]Ruth’s Children’s Hospital-Technion, Haifa, Israel
                [8 ]GRID grid.412881.6, ISNI 0000 0000 8882 5269, Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, , Universidad de Antioquia UdeA, ; Medellin, Colombia
                [9 ]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, MD USA
                [10 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Dr von Hauner Children’s Hospital, , Ludwig-Maximilians-University Munich, ; Munich, Germany
                [11 ]GRID grid.265073.5, ISNI 0000 0001 1014 9130, Department of Pediatrics and Developmental Biology, , Tokyo Medical and Dental University (TMDU), ; Tokyo, Japan
                [12 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Pediatrics, , University of Washington and Seattle Children’s Research Institute, ; Seattle, WA USA
                [13 ]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
                [14 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, , APHP, ; Paris, France
                [15 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Paris University, Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR1163, Imagine Institute, Necker Hospital for Sick Children, ; 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, CA 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, NY USA
                [18 ]GRID grid.413575.1, ISNI 0000 0001 2167 1581, Howard Hughes Medical Institute, ; New York, NY 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, PA USA
                Author information
                http://orcid.org/0000-0002-5360-5180
                Article
                737
                10.1007/s10875-019-00737-x
                7082301
                31953710
                c271765c-4e52-40d4-bd79-db5236c1a043
                © The Author(s) 2020, corrected publication 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
                : 4 November 2019
                : 18 December 2019
                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,next-generation sequencing

                Comments

                Comment on this article