Purpose: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs.
Methods: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs.
Results: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor.
Conclusion: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035476 | PMC |
| http://dx.doi.org/10.1007/s10875-024-01708-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons.
J Clin Immunol
November 2024
Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.
Purpose: The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear.
Methods: We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020.
Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.
J Exp Med
December 2024
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.
Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections.
View Article and Find Full Text PDFQuality-controlled characterization of a monoclonal antibody specific to an EC5-domain of human desmoglein 3 for pemphigus research.
Front Immunol
October 2024
Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
Background: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 auto-abs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community.
View Article and Find Full Text PDFIncontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases.
J Exp Med
November 2024
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, Paris, France.
Article Synopsis
- * A study examined 131 female patients with X-linked dominant incontinentia pigmenti (IP), finding that 36% produced autoantibodies against IFN-α and/or IFN-ω, significantly higher than age-matched controls.
- * The presence of these autoantibodies is linked to an abnormally small thymus and predisposes patients to life-threatening viral infections, while those without these autoantibodies do not face the same risk.
Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.
J Exp Med
October 2024
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.
Article Synopsis
- Tick-borne encephalitis virus (TBEV), spread through tick bites, mostly causes mild illness in over 90% of cases, but can lead to varying degrees of encephalitis in some individuals.
- Around 10% of patients with severe TBE in Austria, Czech Republic, and France have auto-antibodies (auto-Abs) that neutralize certain types of interferon (IFN), which are important for immune response, while only about 1% of patients with milder symptoms have them.
- The presence of these auto-Abs significantly increases the risk of severe TBE, with odds ratios indicating up to a 20.8 times higher chance of severe illness when these auto-Abs are
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!