Inborn error of WAS presenting with SARS-CoV-2-related multisystem inflammatory syndrome in children DOI Creative Commons
Enrico Drago, Francesca Fioredda, Federica Penco

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 6, 2023

Abstract Multisystem inflammatory syndrome in children (MIS-C) has been reported patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case MIS-C a child affected by Wiskott-Aldrich (WAS) gene mutation, elucidating underlying predisposing factors and involved pathways. Genetic analysis revealed frameshift truncating variant WAS gene, resulting protein expression between mild severe forms, despite clinical phenotype resembling X-linked thrombocytopenia (XLT). IL-1β secretion LPS-stimulated peripheral blood mononuclear cells from patient during was lower compared to healthy subjects but increased follow-up. Conversely, percentage ASC (apoptosis-associated speck-like containing CARD) specks patient's circulating monocytes acute phase higher than subjects. The type I interferon (IFN) score normal, contrast raised IFN signature measured far event. This confirms association IEI MIS-C, potentially linked delayed immune responses SARS-CoV-2. XLT underlies subclinical immunodysregulation involving NLRP3 inflammasome type-I response.

Language: Английский

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
Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19 DOI
R. K. Subbarao Malireddi, Bhesh Raj Sharma, Thirumala‐Devi Kanneganti

et al.

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 615 - 645

Published: June 28, 2024

The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. innate immune system is first line of defense against infections, including detection and response Here, we discuss mechanisms that sense coronaviruses, with focus on infection how these protective responses can become detrimental severe cases COVID-19, contributing cytokine storm, inflammation, long-COVID, other complications. We also highlight complex cross talk among cytokines cellular components system, which aid viral clearance but contribute inflammatory cell death, organ damage pathogenesis. Furthermore, evades key enhance its virulence pathogenicity, as well immunity be therapeutically targeted part vaccination treatment strategy. Overall, comprehensive understanding been crucial fight infections development novel host-directed immunotherapeutic strategies for various diseases.

Language: Английский

Citations

12
Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease DOI Creative Commons
Charles E. Samuel

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(8), P. 104960 - 104960

Published: June 24, 2023

A novel coronavirus now known as SARS-CoV-2 emerged in late 2019, possibly following a zoonotic crossover from present bats. This virus was identified the pathogen responsible for severe respiratory disease, disease-19 (COVID-19), which of May 2023, has killed an estimated 6.9 million people globally according to World Health Organization. The interferon (IFN) response, cornerstone antiviral innate immunity, plays key role determining outcome infection by SARS-CoV-2. review considers evidence that leads IFN production; replication is sensitive action; molecular mechanisms antagonizes and how genetic variability human host affects response at level production or action both. Taken together, current understanding suggests deficiency effective important determinant underlying some cases critical COVID-19 disease IFNλ IFNα/β have potential therapeutics treatment infection.

Language: Английский

Citations

23
Life-threatening infections in human newborns: Reconciling age-specific vulnerability and interindividual variability DOI
A. Borghesi

Cellular Immunology, Journal Year: 2024, Volume and Issue: 397-398, P. 104807 - 104807

Published: Jan. 13, 2024

Language: Английский

Citations

4
A Novel Case of IFNAR1 Deficiency Identified a Common Canonical Splice Site Variant in DOCK8 in Western Polynesia: The Importance of Validating Variants of Unknown Significance in Under-Represented Ancestries DOI Creative Commons

Aimee Huynh,

Paul Gray,

Anna Sullivan

et al.

Journal of Clinical Immunology, Journal Year: 2024, Volume and Issue: 44(8)

Published: Aug. 5, 2024

Abstract Advanced genomic technologies such as whole exome or genome sequencing have improved diagnoses and disease outcomes for individuals with genetic diseases. Yet, variants of unknown significance (VUS) require rigorous validation to establish causality modification, exclude them from further analysis. Here, we describe a young individual Polynesian ancestry who in the first 13 mo life presented SARS-CoV-2 pneumonia, severe enterovirus meningitis adenovirus gastroenteritis, adverse reaction MMR vaccination. Genomic analysis identified previously reported pathogenic homozygous variant IFNAR1 (c.1156G > T, p.Glu386* LOF), which is common Western Polynesia. Moreover, new putatively deleterious canonical splice site DOCK8 was also found homozygosity (c.3234 + 2T C). This Polynesians other under-represented ancestries large databases. Despite silico bioinformatic predictions, extensive vitro ex vivo revealed likely be neutral. Thus, our study reports novel case deficiency, but highlights importance functional VUS, including those predicted deleterious, pressing need expand knowledge architecture landscape populations ancestries.

Language: Английский

Citations

2
Long COVID: An Epidemic within the Pandemic DOI Creative Commons
Camilla Mattiuzzi, Giuseppe Lippi

COVID, Journal Year: 2023, Volume and Issue: 3(5), P. 773 - 776

Published: May 19, 2023

Coronavirus disease 2019 (COVID-19), a life-threatening infectious caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in the Chinese city of Wuhan late and has subsequently spread worldwide, reaching pandemic proportions [...]

Language: Английский

Citations

5
Human genetic and immunological determinants of SARS-CoV-2 infection and multisystem inflammatory syndrome in children DOI
Halima Kholaiq,

Yousra Abdelmoumen,

Abderrahmane Moundir

et al.

Clinical & Experimental Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact SARS-CoV-2 infection varies widely, ranging from mild symptoms life-threatening illness organ failure, a higher incidence men than women. Approximately 3 5% critical COVID-19 under 60 smaller percentage elderly exhibit genetic defects IFN-I production, including X-chromosome-linked TLR7 autosomal TLR3 deficiencies. Around 15 20% cases over 70 years old, younger patients, present preexisting autoantibodies neutralizing interferons. Additionally, innate affecting the control response have been associated pediatric multisystem inflammatory (MIS-C). Several studies described rare immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, RNASEL, underlying factors MIS-C susceptibility. However, further investigations expanded patient cohorts are needed validate these findings pave way for new approaches MIS-C. This review aims recent evidence scientific literature on immunological abnormalities predisposing individuals through IFN-I. We will also discuss children Understanding mechanisms pathogenesis severe may inform personalized care population protection strategies against future serious viral infections.

Language: Английский

Citations

1
Kawasaki Disease and Inborn Errors of Immunity: Exploring the Link and Implications DOI Creative Commons
Saniya Sharma,

Pallavi Nadig,

Rakesh Kumar Pilania

et al.

Diagnostics, Journal Year: 2023, Volume and Issue: 13(13), P. 2151 - 2151

Published: June 23, 2023

The exact etiopathogenesis of Kawasaki disease (KD), the most common childhood vasculitis, remains unknown; however, an aberrant immune response, possibly triggered by infectious or environmental agent in genetically predisposed children, is believed to be underlying pathogenetic mechanism. Patients with inborn errors immunity (IEI) are infections that trigger dysregulation due imbalance various arms system. KD may develop as a complication both primary and secondary immunodeficiencies. occur either at presentation have later onset IEIs. These include X-linked agammaglobulinemia (XLA), selective IgA deficiency, transient hypogammaglobulinemia infancy; Wiskott–Aldrich syndrome (WAS), hyper IgE (HIES); chronic granulomatous (CGD), innate intrinsic defects, autoinflammatory diseases, including PFAPA. Hitherto, association between IEI confined specific case reports series and, thus, requires extensive research for comprehensive understanding pathophysiological mechanisms. IEIs serve excellent models would open new insights into pathogenesis children affected KD. current review highlights this critical supported published literature.

Language: Английский

Citations

2
Inborn Error of WAS Presenting with SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children DOI
Enrico Drago, Francesca Fioredda, Federica Penco

et al.

Journal of Clinical Immunology, Journal Year: 2024, Volume and Issue: 45(1)

Published: Nov. 25, 2024

Language: Английский

Citations

0
Multisystemic Inflammatory Syndrome Temporally Associated with COVID-19 in a Regional Pediatric Hospital from México DOI Creative Commons

Joel Barroso-Santos,

Angelina Ingrid Robledo-Martínez, Sara Elva Espinosa‐Padilla

et al.

Pediatric Reports, Journal Year: 2023, Volume and Issue: 15(2), P. 341 - 348

Published: May 26, 2023

Multisystemic inflammatory syndrome (MIS-C) is an condition temporally associated with COVID-19 in children; nevertheless, the clinical and immunologic spectrum of MIS-C heterogeneous, its long-term effects are unknown. During period August 2020 to December 2021, a total 52 cases were confirmed pediatric patients from Hospital del Niño DIF Hidalgo, diagnosed using criteria World Health Organization. All had serologic IgG confirmation SARS-CoV2, mean age was 7 years, 94% did not have previous underlying disease. In addition presentation lymphopenia, neutropenia, thrombocytopenia, elevations D-dimer ferritin levels observed all patients. There improvement intravenous gamma globulin corticosteroid treatment.

Language: Английский

Citations

0