Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee
Stuart G Tangye 1 2, Waleed Al-Herz 3, Aziz Bousfiha 4, Charlotte Cunningham-Rundles 5, Jose Luis Franco 6, Steven M Holland 7, Christoph Klein 8, Tomohiro Morio 9, Eric Oksenhendler 10, Capucine Picard 11 12, Anne Puel 13 14, Jennifer Puck 15, Mikko R J Seppänen 16, Raz Somech 17, Helen C Su 7, Kathleen E Sullivan 18, Troy R Torgerson 19, Isabelle Meyts 20
Affiliations
Affiliations
- Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, 2010, Australia. s.tangye@garvan.org.au.
- St Vincent's Clinical School, Faculty of Medicine & Health, UNSW Sydney, Darlinghurst, NSW, Australia. s.tangye@garvan.org.au.
- Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
- Laboratoire d'Immunologie Clinique, d'Inflammation et d'Allergy LICIA Clinical Immunology Unit, Casablanca Children's Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco.
- Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
- Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de Antioquia UdeA, Medellin, Colombia.
- Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
- Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
- Department of Clinical Immunology, Hôpital Saint-Louis, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
- Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, APHP, Paris, France.
- Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR1163, Imagine Institute, Necker Hospital for Sick Children, Université Paris Cité, Paris, France.
- Laboratory of Human Genetics of Infectious Diseases, INSERM U1163, Necker Hospital, 75015, Paris, France.
- Université Paris Cité, Imagine Institute, 75015, Paris, France.
- Department of Pediatrics, University of California San Francisco and UCSF Benioff Children's Hospital, San Francisco, CA, USA.
- Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center and Rare Diseases Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Pediatric Department and Immunology Unit, Sheba Medical Center, Tel Aviv, Israel.
- Division of Allergy Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Allen Institute for Immunology, Seattle, WA, USA.
- Department of Immunology and Microbiology, Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and KU Leuven, 3000, Leuven, Belgium.
Abstract
We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (published January 2020) or were characterized earlier but have since been confirmed or expanded in subsequent studies. While variants in additional genes associated with immune diseases have been reported in the literature, this update includes only those that the committee assessed that reached the necessary threshold to represent novel inborn errors of immunity. There are now a total of 485 inborn errors of immunity. These advances in discovering the genetic causes of human immune diseases continue to significantly further our understanding of molecular, cellular, and immunological mechanisms of disease pathogenesis, thereby simultaneously enhancing immunological knowledge and improving patient diagnosis and management. This report is designed to serve as a resource for immunologists and geneticists pursuing the molecular diagnosis of individuals with heritable immunological disorders and for the scientific dissection of cellular and molecular mechanisms underlying monogenic and related human immune diseases.
Keywords: IUIS Committee update; Inborn errors of immunity; autoinflammatory disorders; immune dysregulation; primary immunodeficiencies.
References
https://pubmed.ncbi.nlm.nih.gov/