Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency DOI Creative Commons
Tessa M. Campbell, Zhiyong Liu, Qian Zhang

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(7)

Published: June 7, 2022

Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, clinical features of seven IRF7-deficient from six families five ancestries. Five were homozygous two compound heterozygous for variants. Patients typically had one episode pulmonary viral disease. Age at onset surprisingly broad, 6 mo to 50 yr (mean age 29 yr). respiratory viruses implicated included SARS-CoV-2, virus, syncytial adenovirus. Serological analyses indicated previous infections many common viruses. Cellular revealed strong antiviral immunity expanded populations influenza- SARS-CoV-2-specific memory CD4+ CD8+ T cells. individuals are prone tract but otherwise healthy, potentially due residual IFN-β compensatory adaptive immunity.

Language: Английский

COVID-19 and liver disease DOI
Jean‐François Dufour, Thomas Marjot, Chiara Becchetti

et al.

Gut, Journal Year: 2022, Volume and Issue: 71(11), P. 2350 - 2362

Published: June 14, 2022

Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review manifestations pathophysiological aspects related to patients without disease as well impact of with chronic (CLD), particularly cirrhosis transplantation (LT). been associated overt proinflammatory cytokine profile, which probably contributes substantially observed early late abnormalities. CLD, decompensated cirrhosis, should be regarded a risk factor for severe death. LT was impacted pandemic, mainly due concerns regarding donation recipients. However, did not represent per se worse outcome. Even though scarce, data specific therapy special populations such recipients seem promising. vaccine-induced immunity seems impaired CLD recipients, advocating revised schedule vaccine administration this population.

Language: Английский

Citations

71
Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria DOI Creative Commons
Jérémie Rosain, Anna‐Lena Neehus, Jérémy Manry

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 621 - 645.e33

Published: Feb. 1, 2023

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn IFN-α/β-dependent intrinsic viral diseases. Both types IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria related intramacrophagic pathogens. These have no history severe disease, despite exposure to many viruses, including SARS-CoV-2, which is in individuals impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated vitro, IRF1-dependent responses IFN-γ are, both quantitatively qualitatively, much stronger than those IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control pathogens normally when IFN-γ. By contrast, nine almost normal fibroblasts. Human essential for mycobacteria, but largely redundant antiviral

Language: Английский

Citations

66
Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency DOI Creative Commons
Tom Le Voyer, Audrey V. Parent, Xian Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 623(7988), P. 803 - 813

Published: Nov. 8, 2023

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report patients NIK or RELB deficiency, specific of autosomal-dominant NF-κB2 also have neutralizing against IFNs and are at higher risk getting pneumonia. In these found only in individuals who heterozygous for variants associated both transcription (p52 activity) loss function (LOF) due impaired p100 processing generate p52, regulatory (IκBδ gain (GOF) the accumulation unprocessed p100, therefore increasing inhibitory activity IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, not NFKB2 causing haploinsufficiency p52 p52LOF/IκBδLOF) gain-of-function p52GOF/IκBδLOF). contrast APS-1, disorders NIK, very few tissue-specific autoantibodies. However, their thymuses an abnormal structure, AIRE-expressing medullary thymic epithelial cells. Human inborn errors alternative NF-κB pathway impair development cells, thereby underlying production viral diseases.

Language: Английский

Citations

66
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients DOI Creative Commons
Adrian Gervais, Francesca Rovida, Maria Antonietta Avanzini

et al.

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(9)

Published: June 22, 2023

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis <1% of infected individuals. We show that ∼35% patients hospitalized for WNV disease (WNVD) six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence these antibodies highest with (∼40%), silent as low general population. odds ratios WNVD relative to those without them population range 19.0 (95% CI 15.0–24.0, P value <10–15) only 100 pg/ml IFN-ω 127.4 (CI 87.1–186.4, both at a concentration 10 ng/ml. These block protective effect Vero cells vitro. Auto-Abs underlie ∼40% cases encephalitis.

Language: Английский

Citations

63
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 DOI Creative Commons
Daniela Matuozzo, Estelle Talouarn, Astrid Marchal

et al.

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: April 5, 2023

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent interferon (IFN) immunity or autoantibodies against IFN, account for 15–20% cases life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants remain be identified ~ 80% cases. Methods report here a genome-wide rare variant burden association analysis 3269 patients with COVID-19, 1373 SARS-CoV-2-infected individuals without pneumonia. Among 928 tested quarter (234) were positive excluded. Results No gene reached significance. Under recessive model, most significant at-risk variants was TLR7 , an OR 27.68 (95%CI 1.5–528.7, P = 1.1 × 10 −4 ) biochemically loss-of-function (bLOF) variants. replicated enrichment predicted LOF (pLOF) at 13 influenza susceptibility loci involved TLR3-dependent (OR 3.70[95%CI 1.3–8.2], 2.1 ). This further strengthened by (1) adding recently TYK2 loci, particularly under model 19.65[95%CI 2.1–2635.4], 3.4 −3 ), (2) considering as pLOF branchpoint potentially strong impacts on splicing among 15 4.40[9%CI 2.3–8.4], 7.7 −8 Finally, pLOF/bLOF these significantly younger (mean age [SD] 43.3 [20.3] years) than other (56.0 [17.3] years; 1.68 −5 Conclusions Rare genes can underlie inheritance, 60 years old.

Language: Английский

Citations

59
Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria DOI
Quentin Philippot, Masato Ogishi, Jonathan Bohlen

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(80)

Published: Feb. 3, 2023

Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) IL-17A/F production. We report six patients from four kindreds AR IL-23R deficiency. These are homozygous for one of different loss-of-function IL23R variants. All have a history MSMD, but only two suffered CMC. show that IL-23 induces IL-17A in MAIT cells, possibly contributing the incomplete penetrance CMC unresponsive IL-23. By contrast, is required both baseline and Mycobacterium -inducible immunity Vδ2 + γδ T probably higher MSMD these patients. Human appears contribute IL-17A/F–dependent Candida single lymphocyte subset IFN-γ–dependent at least subsets.

Language: Английский

Citations

48
Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs DOI Creative Commons
Jean‐Laurent Casanova, Mark S. Anderson

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(3)

Published: Jan. 31, 2023

Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing IFNs due to autoimmune regulator (AIRE)-driven T cell tolerance were discovered in 2006, but not initially linked any disease. These two lines clinical investigation converged 2020, with the discovery that inherited and/or deficiencies accounted for approximately 15%-20% cases critical COVID-19 pneumonia unvaccinated individuals. Thus, insufficient at onset SARS-CoV-2 infection may be general determinant life-threatening COVID-19. findings illustrate unpredictable, considerable, contribution study genetic diseases basic biology and public health.

Language: Английский

Citations

45
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children DOI Creative Commons
Paul Bastard, Adrian Gervais, Maki Taniguchi

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(2)

Published: Jan. 4, 2024

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only three, plus IFN-ω five, and IFN-α2, IFN-β two; nine patients). Seven (3.8%) Abs at least ng/ml one IFN, whereas the other 12 (6.6%) 100 pg/ml. The auto-Abs neutralized both unglycosylated glycosylated IFNs. also detected pg/ml 4 2,267 uninfected (0.2%) 45 (2%). odds ratios (ORs) life-threatening were, therefore, higher (OR [95% CI] = 67.6 [5.7-9,196.6]) than 2.6 [1.2-5.3]). ORs were high concentrations 12.9 [4.6-35.9]) those low 5.5 [3.1-9.6]) and/or IFN-α2.

Language: Английский

Citations

24
Pharmacological Activities of Plant‐Derived Fraxin with Molecular Mechanisms: A Comprehensive Review DOI
Jannatul Ferdous, Md. Shimul Bhuia, Raihan Chowdhury

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(5)

Published: March 20, 2024

Abstract Fruits and vegetables serve not only as sources of nutrition but also medicinal agents for the treatment diverse diseases maladies. These dietary components are significant resources phytochemicals that demonstrate therapeutic properties against many illnesses. Fraxin is a naturally occurring coumarin glycoside mainly present in various species Fraxinus genera, having multitude uses disorders. This study focuses to investigate pharmacological activities, botanical sources, biopharmaceutical profile phytochemical fraxin based on different preclinical non‐clinical studies show scientific evidence evaluate underlying molecular mechanisms effects ailments. For this, data was searched collected (as February 15, 2024) variety credible electronic databases, including PubMed/Medline, Scopus, Springer Link, ScienceDirect, Wiley Online, Web Science, Google Scholar. The findings demonstrated favorable outcomes relation range or medical conditions, inflammation, neurodegenerative disorders such cerebral ischemia‐reperfusion (I/R) depression, viral infection, well diabetic nephropathy. showed protective osteoprotective, renoprotective, pulmoprotective, hepatoprotective, gastroprotective due its antioxidant capacity. has great capability diminish oxidative stress‐related damage organs by stimulating enzymes, downregulating nuclear factor kappa B NLRP3, triggering Nrf2/ARE signaling pathways. exhibited poor oral bioavailability because reduced absorption wide distribution into tissues organs. However, extensive research required decipher profiles, clinical necessary establish efficacy natural compound reliable agent.

Language: Английский

Citations

19
Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine DOI Creative Commons
Yanhong Duo, Lei Han, Yaoqiang Yang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(20), P. 11242 - 11347

Published: Oct. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

Language: Английский

Citations

19