Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α DOI Open Access
Alexis Mathian, Paul Breillat, Karim Dorgham

et al.

Annals of the Rheumatic Diseases, Journal Year: 2022, Volume and Issue: 81(12), P. 1695 - 1703

Published: Aug. 16, 2022

Objectives Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. Methods We retrospectively analysed a monocentric longitudinal cohort 609 SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed abolishment Madin-Darby bovine kidney cell protection IFN-α2 vesicular stomatitis virus challenge. Serum-neutralising activity IFN-α2, was determined reporter luciferase assay. SARS-CoV-2 antibody responses measured wild-type spike antigen, while serum-neutralising the historical strain variants concerns. Results Neutralising non-neutralising anti-IFN-α antibodies present at frequency 3.3% 8.4%, respectively, individuals unlike AAbs, associated reduced serum levels likelihood to develop active disease. However, they predispose an increased risk herpes zoster severe pneumonia. Severe pneumonia SLE is mostly combined neutralisation different IFNs-I. Finally, do not interfere vaccine humoral immunogenicity. Conclusion The production anti-IFN-I likely be consequence SLE-associated high IFN-I levels, beneficial effect disease activity, yet greater viral risk. This finding reinforces recommendations for vaccination

Language: Английский

Human genetic and immunological determinants of critical COVID-19 pneumonia DOI Open Access
Qian Zhang, Paul Bastard, Adem Karbuz

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 587 - 598

Published: Jan. 28, 2022

Language: Английский

Citations

323
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies DOI Creative Commons
Jérémy Manry, Paul Bastard, Adrian Gervais

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(21)

Published: May 16, 2022

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased infection fatality rate at all ages, men women. Autoantibodies common predictors COVID-19. Testing for should be considered population.

Language: Английский

Citations

160
Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs DOI Creative Commons
Stephanie Seneff, Greg Nigh, Anthony M. Kyriakopoulos

et al.

Food and Chemical Toxicology, Journal Year: 2022, Volume and Issue: 164, P. 113008 - 113008

Published: April 15, 2022

The mRNA SARS-CoV-2 vaccines were brought to market in response the public health crises of Covid-19. utilization context infectious disease has no precedent. many alterations vaccine hide from cellular defenses and promote a longer biological half-life high production spike protein. However, immune is very different that infection. In this paper, we present evidence vaccination induces profound impairment type I interferon signaling, which diverse adverse consequences human health. Immune cells have taken up nanoparticles release into circulation large numbers exosomes containing protein along with critical microRNAs induce signaling recipient at distant sites. We also identify potential disturbances regulatory control synthesis cancer surveillance. These potentially causal link neurodegenerative disease, myocarditis, thrombocytopenia, Bell's palsy, liver impaired adaptive immunity, DNA damage tumorigenesis. show VAERS database supporting our hypothesis. believe comprehensive risk/benefit assessment questions them as positive contributors

Language: Английский

Citations

152
Immunology of SARS-CoV-2 infection in children DOI Open Access
Janet Chou, Paul G. Thomas, Adrienne G. Randolph

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 177 - 185

Published: Feb. 1, 2022

Language: Английский

Citations

145
Mechanisms of viral inflammation and disease in humans DOI
Jean‐Laurent Casanova, Laurent Abel

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1080 - 1086

Published: Nov. 25, 2021

Disease and accompanying inflammation are uncommon outcomes of viral infection in humans. Clinical occurs if steady-state cell-intrinsic leukocytic immunity to viruses fails. Inflammation attests the attempts newly recruited activated leukocytes resolve blood or tissues. In confusing battle between a myriad cells, studies human genetics can separate root cause disease from its consequences. Single-gene inborn errors underlying diverse infections skin, brain, lungs help clarify determinants disease. The genetic elucidation immunological deficits single patient with specific vulnerability profile reveal mechanisms that may be triggered by other causes, inherited otherwise, patients. This dissection is giving rise new biology medicine.

Language: Английский

Citations

122
The intersection of COVID-19 and autoimmunity DOI Open Access
Jason S. Knight, Roberto Caricchio, Jean‐Laurent Casanova

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(24)

Published: Oct. 28, 2021

Acute COVID-19, caused by SARS-CoV-2, is characterized diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute pathogenesis of severe COVID-19. Researchers working at intersection COVID-19 autoimmunity recently gathered an American Autoimmune Related Diseases Association Noel R. Rose Colloquium address current state knowledge regarding two important questions: Does established predispose COVID-19? And, same time, can SARS-CoV-2 trigger de novo autoimmunity? Indeed, work date demonstrated 10% 15% patients critical pneumonia exhibit autoantibodies against type I interferons, suggesting preexisting underlies disease in some patients. Other studies have identified functional following such as those promote thrombosis or antagonize cytokine signaling. These may arise a predominantly extrafollicular B cell response more prone generating autoantibody-secreting cells. This Review highlights understanding, evolving concepts, unanswered questions provided this unique opportunity determine mechanisms which viral be exacerbated by, even trigger, autoimmunity. The potential role post-acute sequelae also discussed.

Language: Английский

Citations

111
Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells DOI Creative Commons
Rémi Planès, Miriam Pinilla, Karin Santoni

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(13), P. 2385 - 2400.e9

Published: May 16, 2022

Language: Английский

Citations

109
From rare disorders of immunity to common determinants of infection: Following the mechanistic thread DOI Creative Commons
Jean‐Laurent Casanova, Laurent Abel

Cell, Journal Year: 2022, Volume and Issue: 185(17), P. 3086 - 3103

Published: Aug. 1, 2022

The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria seasonal influenza virus have inspired studies two common infections: tuberculosis COVID-19. A TYK2 genotype impairing production accounts for about 1% cases, autoantibodies neutralizing account 15% critical COVID-19 cases. discovery inborn mechanisms drove the identification monogenic or autoimmune determinants related infections. This “rare-to-common” genetic mechanistic approach to infectious diseases may be heuristic value.

Language: Английский

Citations

106
Human autoantibodies underlying infectious diseases DOI Creative Commons
Anne Puel, Paul Bastard, Jacinta Bustamante

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(4)

Published: March 23, 2022

The vast interindividual clinical variability observed in any microbial infection—ranging from silent infection to lethal disease—is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of corresponding cytokine or response pathway. against type I IFNs COVID-19 pneumonia adverse reactions live attenuated yellow fever virus vaccine. II IFN severe disease caused environmental tuberculous mycobacteria, other intra-macrophagic microbes. IL-17A/F IL-6 are less common mucocutaneous candidiasis staphylococcal diseases, respectively. Inborn autoantibodies GM-CSF pulmonary alveolar proteinosis; associated infections well characterized. In individual patients, preexist with pathogen concerned disease. Human antibody-driven autoimmunity can interfere that essential for protective immunity agents but otherwise redundant, thereby underlying diseases.

Language: Английский

Citations

96
COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences DOI Creative Commons
Felix Scholkmann,

Christian-Albrecht May

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 246, P. 154497 - 154497

Published: May 3, 2023

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and 13 billion COVID-19 vaccine doses administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome 2 (SARS-CoV-2) can lead an disease, i.e. COVID-19, but also a post-acute (PACS, "long COVID"). Currently, side effects vaccines are increasingly being noted studied. Here, we summarise currently available indications discuss our conclusions that (i) these specific similarities differences PACS, (ii) new term should be used refer (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), (iii) is need distinguish between (ACVS) (PACVS) - in analogy PACS ("long Moreover, address mixed forms caused by natural SARS-CoV-2 vaccination. We explain why it important for medical diagnosis, care research use terms (PCVS, ACVS PACVS) order avoid confusion misinterpretation underlying causes enable optimal therapy. do not recommend "Post-Vac-Syndrome" imprecise. The article serves current problem "medical gaslighting" relation PCVS raising awareness among professionals supplying appropriate terminology disease.

Language: Английский

Citations

92