ArticleNature medicine2016
Identification of a major epitope by anti-interferon-γ autoantibodies in patients with mycobacterial disease.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.
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Who cites it
72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Anti-interferon-γ autoantibodies syndrome and opportunistic infections: systematic literature review.Frontiers in immunology · 2025Pooled it
- Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.Journal of clinical immunology · 2023Pooled it
- Pathogen spectrum and immunotherapy in patients with anti-IFN-γ autoantibodies: A multicenter retrospective study and systematic review.Frontiers in immunology · 2022Pooled it
- Highly neutralizing anti-IFN-ω autoantibodies underlie severe pediatric adenovirus infection.Journal of human immunity · 2026Article
- Quantitative measurement of anti-interferon-gamma autoantibodies for routine laboratory implementation.iScience · 2026Article
- Prospective Registry of Outcomes, Treatment, and Clinical Trajectories for Anti-IFN-γ Immunodeficiency.JAMA network open · 2026Article
- Interleukin-6 fromMicrobiology spectrum · 2026Article
- Identification and characterization of bone marrow plasma cells producing IFN-γ-neutralizing autoantibodies in adult-onset immunodeficiency.Cell reports. Medicine · 2026Article
- Anti-interferon-γ autoantibodies: immunopathogenesis, diagnostic innovation, and emerging therapeutic strategies in an adult-onset immunodeficiency.Frontiers in immunology · 2026Review
- Article
- SevereInfection and drug resistance · 2026Article
- Cervical Mycobacterium genavense infection in a patient with lymphadenitis and previously unknown anti-IFN-γ IgG autoantibodies.Infection · 2025Article
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design.The Journal of experimental medicine · 2025Article
- Deepening Understanding of the Clinical Features and Diagnostic Approaches to Anti-Interferon-Gamma Autoantibody Associated Adult-Onset Immunodeficiency in the Last 20 Years: A Case Report and Literature Review.Journal of clinical immunology · 2025Review
- Mechanisms of antibody-dependent enhancement of infectious disease.Nature reviews. Immunology · 2025Review
- Upregulation of interferon-γ activation in patients with anti-interferon-γ autoantibodies immunodeficiency syndrome: insights from single-cell analysis.Frontiers in immunology · 2025Article
- Article
- Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies.Immune network · 2024Article
- Th1 cell immune response inMicrobiology spectrum · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The binding of autoantibodies (autoAbs) to interferon (IFN)-γ in people with mycobacterial diseases has become an emerging medical concern. Many patients display specific human leukocyte antigen (HLA) class II haplotypes, which suggests that a common T cell-dependent and B cell-dependent mechanism might underlie the production of specific anti-IFN-γ autoAbs. We show here that these autoAbs target a major epitope (amino acids 121-131, designated position (P)121-131) in a region crucial for IFN-γ receptor (IFN-γR) activation to impair IFN-γ-mediated activities. The amino acid sequence of this epitope is highly homologous to a stretch in the Noc2 protein of Aspergillus spp., which was cross-reactive with autoAbs from patients. Rats immunized with Aspergillus Noc2 developed antibodies that reacted with human IFN-γ. We generated an epitope-erased variant of IFN-γ (EE-IFN-γ), in which the major neutralizing epitope region was altered. The binding affinity of anti-IFN-γ autoAbs for EE-IFN-γ was reduced by about 40%, as compared to that for IFN-γ1-131. Moreover, EE-IFN-γ activated the IFN-γR downstream signaling pathway ex vivo, irrespectively of anti-IFN-γ autoAbs. In conclusion, we identified a common, crucial B cell epitope that bound to anti-IFN-γ autoAbs in patients, and we propose a molecular-mimicry model for autoAb development. In addition, treatment with EE-IFN-γ might be worth investigating in patients producing anti-IFN-γ autoAbs.
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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 OpenQuestion graph.