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

NEMO-NDAS

(2022) Shaymaa Hegazy et al.   AMERICAN JOURNAL OF DERMATOPATHOLOGY

TLR8 / TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins

(2022) Martina Fejtkova et al.   AMERICAN JOURNAL OF HEMATOLOGY

Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human

(2022) Gan Sun et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Case Report: X-Linked SASH3 Deficiency Presenting as a Common Variable Immunodeficiency

(2022) Moisés Labrador-Horrillo et al.   Frontiers in Immunology

Gain-of-function IKZF1 variants in humans cause immune dysregulation associated with abnormal T/B cell late differentiation

(2022) Akihiro Hoshino et al.   Science Immunology

RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis

(2021) Artem Kalinichenko et al.   BLOOD

Loss of DIAPH1 causes SCBMS, combined immunodeficiency and mitochondrial dysfunction

(2021) Meri Kaustio et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Agammaglobulinemia with normal B-cell numbers in a patient lacking Bob1

(2021) Patrick Kury et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor

(2021) Shinsuke Kataoka et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex

(2021) Wayne Bainter et al.   JOURNAL OF CLINICAL INVESTIGATION

Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening

(2021) Ryan M. Baxley et al.   Nature Communications

SASH3 variants cause a novel form of X-linked combined immunodeficiency with immune dysregulation

(2021) Ottavia M. Delmonte et al.   BLOOD

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

(2021) Stefano Vavassori et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

(2021) Jesús Troya et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients

(2021) Carole Le Coz et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice

(2021) Lin Wang et al.   NATURE GENETICS

Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease

(2021) Tom Le Voyer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

(2021) Hui Hui Wong et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy

(2021) Vivien Béziat et al.   CELL

Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death

(2021) Justin Taft et al.   CELL

Neutralizing type‐I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID‐19

(2021) Michael S Abers et al.   IMMUNOLOGY AND CELL BIOLOGY

Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK

(2021) Veronika Kanderova et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Human Disease Phenotypes Associated with Loss and Gain of Function Mutations in STAT2: Viral Susceptibility and Type I Interferonopathy

(2021) Christopher James Arthur Duncan et al.   JOURNAL OF CLINICAL IMMUNOLOGY

High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency

(2021) Rui Yang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Enhanced cGAS-STING–dependent interferon signaling associated with mutations in ATAD3A

(2021) Alice Lepelley et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation

(2021) Paul M. Tyler et al.   NATURE IMMUNOLOGY

A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS

(2021) Motoi Yamashita et al.   NATURE IMMUNOLOGY

Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child

(2021) Masato Ogishi et al.   NATURE MEDICINE

Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα)

(2021) Wayne Bainter et al.   Science Immunology

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

(2021) Paul Bastard et al.   Science Immunology

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

(2021) Takaki Asano et al.   Science Immunology

Biallelic ZNFX1 variants are associated with a spectrum of immuno‐hematological abnormalities

(2021) Salem Alawbathani et al.   CLINICAL GENETICS

Inborn errors of IKAROS and AIOLOS

(2021) Motoi Yamashita et al.   CURRENT OPINION IN IMMUNOLOGY

Inborn errors of IL-6 family cytokine responses

(2021) Yin-Huai Chen et al.   CURRENT OPINION IN IMMUNOLOGY

Biallelic CXCR2 loss-of-function mutations define a distinct congenital neutropenia entity

(2021) Viviana Marin-Esteban et al.   HAEMATOLOGICA

Pre-existing Autoantibodies Neutralizing High Concentrations of Type I Interferons in Almost 10% of COVID-19 Patients Admitted to Intensive Care in Barcelona

(2021) Xavier Solanich et al.   JOURNAL OF CLINICAL IMMUNOLOGY

X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

(2021) Hassan Abolhassani et al.   JOURNAL OF CLINICAL IMMUNOLOGY

T and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients

(2021) Hye Sun Kuehn et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Heterozygous missense variant of the proteasome subunit β-type 9 causes neonatal-onset autoinflammation and immunodeficiency

(2021) Nobuo Kanazawa et al.   Nature Communications

Biallelic mutations in calcium release activated channel regulator 2A (CRACR2A) cause a primary immunodeficiency disorder

(2021) Beibei Wu et al.   eLife

Germline biallelic mutation affecting the transcription factor Helios causes pleiotropic defects of immunity

(2021) Tala Shahin et al.   Science Immunology

Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells

(2021) Iivo Hetemäki et al.   Science Immunology

Identification of Germline Monoallelic Mutations in IKZF2 in Patients with Immune Dysregulation

(2021) Tala Shahin et al.   Blood Advances

Recent human genetic errors of innate immunity leading to increased susceptibility to infection

(2020) Leen Moens et al.   CURRENT OPINION IN IMMUNOLOGY

Germline biallelic PIK3CG mutations in a multifaceted immunodeficiency with immune dysregulation

(2020) Marini Thian et al.   HAEMATOLOGICA

Severe combined immunodeficiency caused by inositol-trisphosphate 3-kinase B (ITPKB) deficiency

(2020) Abduarahman Almutairi et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Systemic Inflammation and Myelofibrosis in a Patient with Takenouchi-Kosaki Syndrome due to CDC42 Tyr64Cys Mutation

(2020) Giorgia Bucciol et al.   JOURNAL OF CLINICAL IMMUNOLOGY

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

(2020) Aziz Bousfiha et al.   JOURNAL OF CLINICAL IMMUNOLOGY

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

(2020) Stuart G. Tangye et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy

(2020) Conor Gruber et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome

(2020) Yin-Huai Chen et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency

(2020) Scott B. Drutman et al.   NEW ENGLAND JOURNAL OF MEDICINE

PAX1 is essential for development and function of the human thymus

(2020) Yasuhiro Yamazaki et al.   Science Immunology

Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and pre‐excitation syndrome

(2020) Tim Niehues et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

APRIL-dependent lifelong plasmacyte maintenance and immunoglobulin production in humans

(2020) Tzu-Wen Yeh et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

A toxic palmitoylation of Cdc42 enhances NF-κB signaling and drives a severe autoinflammatory syndrome

(2020) Bahia Bekhouche et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction

(2020) Jeffrey M. Verboon et al.   JOURNAL OF CLINICAL IMMUNOLOGY

A New Patient with NOCARH Syndrome Due to CDC42 Defect

(2020) Tingyan He et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Inherited human IFN-γ deficiency underlies mycobacterial disease

(2020) Gaspard Kerner et al.   JOURNAL OF CLINICAL INVESTIGATION

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

(2020) Vivien Béziat et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Whole-genome sequencing of a sporadic primary immunodeficiency cohort

(2020) James E. D. Thaventhiran et al.   NATURE

A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report

(2020) Aleksandra Szczawinska-Poplonyk et al.   Frontiers in Immunology

Germline TET2 Loss-Of-Function Causes Childhood Immunodeficiency And Lymphoma

(2020) Jarmila Stremenova Spegarova et al.   BLOOD

Presence of Genetic Variants Among Young Men With Severe COVID-19

(2020) Caspar I. van der Made et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

A novel STING1 variant causes a recessive form of STING-associated vasculopathy with onset in infancy (SAVI)

(2020) Bin Lin et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation

(2020) Carla Noemi Castro et al.   JOURNAL OF EXPERIMENTAL MEDICINE

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease

(2020) Sarah A. Cook et al.   SCIENCE

The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

(2020) Elisabeth Salzer et al.   Science Immunology

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in Folliculin Interacting Protein 1 deficiency

(2020) Francesco Saettini et al.   BLOOD

Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1

(2020) Pui Y. Lee et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Human NK cell deficiency as a result of biallelic mutations in MCM10

(2020) Emily M. Mace et al.   JOURNAL OF CLINICAL INVESTIGATION

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

(2020) Qian Zhang et al.   SCIENCE

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

(2020) Paul Bastard et al.   SCIENCE

Spotlight on the Replisome: Aetiology of DNA Replication-Associated Genetic Diseases

(2020) Roberto Bellelli et al.   TRENDS IN GENETICS

Early-onset autoimmunity associated with SOCS1 haploinsufficiency

(2020) Jérôme Hadjadj et al.   Nature Communications

Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain-of-function

(2020) Jahnavi Aluri et al.   BLOOD

Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria

(2020) Rui Yang et al.   CELL

Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects

(2020) Atar Lev et al.   JOURNAL OF EXPERIMENTAL MEDICINE

cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing

(2020) Carolina Uggenti et al.   NATURE GENETICS

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease

(2020) David B. Beck et al.   NEW ENGLAND JOURNAL OF MEDICINE

Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans

(2020) Alon Schneider Hait et al.   Science Immunology

Mechanism-Based Precision Therapy for the Treatment of Primary Immunodeficiency and Primary Immunodysregulatory Diseases

(2019) Jennifer W. Leiding et al.   Journal of Allergy and Clinical Immunology-In Practice

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population

(2019) Dorota Monies et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes

(2019) Jérôme Hadjadj et al.   BLOOD

Severe autoinflammation in 4 patients with C-terminal variants in cell division control protein 42 homolog (CDC42) successfully treated with IL-1β inhibition

(2019) Yael Gernez et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Gain-of-function CEBPE mutation causes non-canonical autoinflammatory inflammasomopathy

(2019) Helka Göös et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Flow Cytometric-Based Analysis of Defects in Lymphocyte Differentiation and Function Due to Inborn Errors of Immunity

(2019) Cindy S. Ma et al.   Frontiers in Immunology

Defining a new immune deficiency syndrome: MAN2B2-CDG

(2019) Jan Verheijen et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

(2019) Michael T. Lam et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology

(2019) Andrew J. Takeda et al.   Nature Communications

Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β

(2019) Juan Li et al.   Science Immunology

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

(2019) Adriana A. de Jesus et al.   JOURNAL OF CLINICAL INVESTIGATION

Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease

(2019) Najoua Lalaoui et al.   NATURE

A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1

(2019) Panfeng Tao et al.   NATURE

Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

(2019) Fabien G. Lafaille et al.   NATURE MEDICINE

Somatic Variants: New Kids on the Block in Human Immunogenetics

(2019) L. Van Horebeek et al.   TRENDS IN GENETICS

Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2

(2019) Christopher J. A. Duncan et al.   Science Immunology

What do primary immunodeficiencies tell us about the essentiality/redundancy of immune responses?

(2018) Alain Fischer et al.   SEMINARS IN IMMUNOLOGY

Human genetics of infectious diseases: Unique insights into immunological redundancy

(2018) Jean-Laurent Casanova et al.   SEMINARS IN IMMUNOLOGY

The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies

(2017) Aziz Bousfiha et al.   JOURNAL OF CLINICAL IMMUNOLOGY

International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

(2017) Capucine Picard et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia

(2015) Tetsuya Niihori et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Diseases caused by mutations inORAI1andSTIM1

(2015) Rodrigo S. Lacruz et al.   Annals of the New York Academy of Sciences

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production

(2015) Anja Brehm et al.   JOURNAL OF CLINICAL INVESTIGATION

Contribution of high-throughput DNA sequencing to the study of primary immunodeficiencies

(2014) Capucine Picard et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies

(2014) Jean-Laurent Casanova et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits

(2014) Paul L Auer et al.   NATURE GENETICS

Inborn Errors of Human JAKs and STATs

(2012) Jean-Laurent Casanova et al.   IMMUNITY