ArticleThe Journal of experimental medicine2025
Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- High prevalence of autoantibodies neutralizing type I IFNs in Japanese patients with hepatitis C.Journal of human immunity · 2026Article
- Functional diversity of natural humanScience advances · 2026Article
- Autoantibodies neutralizing type I interferons underlie a third of cases of Chikungunya virus encephalitis or myelitis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.Cell · 2026Article
- Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.Journal of human immunity · 2026Article
- Toward a monogenic architecture of human infections: From 1996 to 2026.Journal of human immunity · 2026Review
- Human antibodies against West Nile and related orthoflaviviruses.bioRxiv : the preprint server for biology · 2026Article
- High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.medRxiv : the preprint server for health sciences · 2026Article
- An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity.Nature cell biology · 2026Article
- Increased prevalence of autoantibodies neutralizing IFNλ2/3 in young individuals with cystic fibrosis.Journal of human immunity · 2026Article
- Autoantibodies neutralizing type I IFNs in a fatal case of H5N1 avian influenza.The Journal of experimental medicine · 2026Article
- Autoantibodies neutralizing type 1 interferons in two cohorts of people with HIV.Journal of human immunity · 2026Article
- Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis.The Journal of experimental medicine · 2026Article
- Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Host Responses to SARS-CoV-2 with an Emphasis on Cytokines.International journal of molecular sciences · 2026Review
- Avidity of autoantibodies against type I interferons as a factor associated with neurological complications in severe COVID-19.Frontiers in immunology · 2026Article
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Autoantibodies neutralizing type I interferons (IFN-Is; IFNα or IFNω) exacerbate severe viral disease, but specific treatments are unavailable. With footprint profiling, we delineate two dominant IFN-I faces commonly recognized by neutralizing IFN-I autoantibody-containing plasmas from aged individuals with HIV-1 and from individuals with severe COVID-19. These faces overlap with IFN-I regions independently essential for engaging the IFNAR1/IFNAR2 heterodimer, and neutralizing plasmas efficiently block the interaction of IFN-I with both receptor subunits in vitro. In contrast, non-neutralizing autoantibody-containing plasmas limit the interaction of IFN-I with only one receptor subunit and display relatively low IFN-I-binding avidities, thus likely hindering neutralizing function. Iterative engineering of signaling-inert mutant IFN-Is (simIFN-Is) retaining dominant autoantibody targets created potent decoys that prevent IFN-I neutralization by autoantibody-containing plasmas and that restore IFN-I-mediated antiviral activity. Additionally, microparticle-coupled simIFN-Is were effective at depleting IFN-I autoantibodies from plasmas, leaving antiviral antibodies unaffected. Our study reveals mechanisms of action for IFN-I autoantibodies and demonstrates a proof-of-concept strategy to alleviate pathogenic effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.