ArticleThe Journal of allergy and clinical immunology2023
NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.
Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.Journal of clinical immunology · 2024Pooled it
- Anti-Type I Interferon Autoantibodies in COVID-19 and Systemic Lupus Erythematosus: A Comparative Review.Antibodies (Basel, Switzerland) · 2026Review
- Heterozygous variants in DOCK2 leading to susceptibility to viral illnesses.The Journal of allergy and clinical immunology · 2026Article
- Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design.The Journal of experimental medicine · 2025Article
- Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.The Journal of experimental medicine · 2025Article
- Article
- Autoimmunity against cytokines: Double strike in autoimmune disease, a historical perspectiveBiomedica : revista del Instituto Nacional de Salud · 2024Review
- Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.The Journal of experimental medicine · 2024Article
- Immune responses in COVID-19 patients: Insights into cytokine storms and adaptive immunity kinetics.Heliyon · 2024Review
- Aire in Autoimmunity.Annual review of immunology · 2024Review
- Yin and yang of interferons: lessons from the coronavirus disease 2019 (COVID-19) pandemic.Current opinion in immunology · 2024Review
- Anti-cytokine autoantibodies: mechanistic insights and disease associations.Nature reviews. Immunology · 2024Review
- TIGITFrontiers in immunology · 2024Article
- Anticytokine Autoantibodies in Infectious Diseases: A Practical Overview.International journal of molecular sciences · 2023Review
- Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis.Journal of translational autoimmunity · 2023Article
- Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- Struggling with COVID-19 in Adult Inborn Errors of Immunity Patients: A Case Series of Combination Therapy and Multiple Lines of Therapy for Selected Patients.Life (Basel, Switzerland) · 2023Article
- Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.JCI insight · 2023Article
- Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients.medRxiv : the preprint server for health sciences · 2023Article
Corrections and comments
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Authors and funding
42 authors at 20 institutions in 2 countries.
Funding
Abstract
backgroundAutoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown.
objectiveWe quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections.
methodsCirculating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control.
resultsAmong 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity.
conclusionsHigh levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.
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