Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

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.

Inborn Errors of Immunity among Egyptian Children with Recurrent Acute Otitis Media

“…IEIs are increasingly diagnosed in high-income countries. 6 However, the burden of IEIs is probably underestimated in low-middle income countries (LMICs), particularly in communities with a high rate of consanguineous marriages, such as the MENA region. This may be attributed to the lack of a nationwide newborn screening program for IEIs and the highly diverse clinical manifestations of IEIs (related to increased susceptibility to infections, autoimmunity, autoinflammation, allergy, and lymphoproliferative/neoplastic diseases), demanding a high index of suspicion.…”

“…16 19 IEIs were defined following the 2019 classification of the International Union of Immunological Societies and 2019 diagnostic criteria of the European Society of Immunodeficiencies, as provided in Supplementary Material (available in the online version). 6 20…”

“…IEIs, previously known as primary immunodeficiency, are a diverse group (more than 400 types) of inherited defects of the immune system, characterized by increased susceptibility to infections and/or immune dysregulation. 6 IEIs are individually rare, but with recent advances in laboratory and molecular techniques, their collective prevalence is estimated to reach 1/1,000 to 1/5,000 of the general population. 6 7 Timely management of IEIs is critical for preventing severe acute and long-term consequences.…”

“…6 IEIs are individually rare, but with recent advances in laboratory and molecular techniques, their collective prevalence is estimated to reach 1/1,000 to 1/5,000 of the general population. 6 7 Timely management of IEIs is critical for preventing severe acute and long-term consequences. However, many IEIs patients remain undiagnosed or have a remarkably delayed diagnosis, which is associated with worse outcome.…”

Impfungen bei Störungen der Immunfunktion

“…Zu den „angeborenen Immundefizienzen“ zählen inzwischen mehr als 400 genetisch bedingte Krankheitsbilder. Gemäß internationaler Klassifikation können diese in 10 Gruppen nach den betroffenen Funktionen des Immunsystems eingeteilt werden 2 . Weil zunehmend erkannt wird, dass die Störungen nicht nur auf Funktionsausfällen, sondern auch auf einer gestörten Regulation des Immunsystems basieren, wird heute auch von „angeborenen Störungen des Immunsystems“ gesprochen.…”