Innate virus-sensing pathways in B cell systemic autoimmunity

Science, Journal Year: 2023, Volume and Issue: 380(6644), P. 478 - 484

Published: May 4, 2023

Although all multicellular organisms have germ line-encoded innate receptors to sense pathogen-associated molecular patterns, vertebrates also evolved adaptive immunity based on somatically generated antigen B and T cells. Because randomly may react with self-antigens, tolerance checkpoints operate limit but not completely prevent autoimmunity. These two systems are intricately linked, playing an instrumental role in the induction of antiviral immunity. In this work, we review how inborn errors can instigate cell Increased nucleic acid sensing, often resulting from defects metabolizing pathways or retroelement control, break converge into TLR7-, cGAS-STING-, MAVS-dominant signaling pathways. The syndromes span a spectrum that ranges chilblain systemic lupus severe interferonopathies.

Language: Английский

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COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2024, Volume and Issue: 44(11), P. 2321 - 2333

Published: Oct. 9, 2024

BACKGROUND: COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration underlying determinants heightened cardiovascular disease MACE post–COVID-19 are not known. METHODS: Data from UK Biobank was used to identify cases (n=10 005) who were positive for polymerase chain reaction (PCR + )-based tests SARS-CoV-2 infection (n=8062) or received hospital-based International Classification Diseases version-10 (ICD-10 ) codes (n=1943) between February 1, 2020 December 31, 2020. Population controls (n=217 730) propensity score—matched (n=38 860) also drawn during same period. Proportional hazard models evaluate association long-term (>1000 days) as a coronary artery equivalent. Additional analyses examined whether interacted genetic affect its components. RESULTS: The elevated in at all levels severity (HR, 2.09 [95% CI, 1.94–2.25]; P <0.0005) greater extent hospitalized 3.85 3.51–4.24]; <0.0005). Hospitalization represented equivalent since incident among without history even higher than that observed patients 1.21 1.08–1.37]; <0.005). A significant interaction ABO locus hospitalization ( =0.01), thrombotic being increased subjects non-O blood types 1.65 1.29–2.09]; =4.8×10 −5 type O 0.96 0.66–1.39]; =0.82). CONCLUSIONS: represents equivalent, post–acute infarction stroke particularly types. These results may have important clinical implications represent, our knowledge, one first examples gene-pathogen exposure events.

Language: Английский

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ABO blood group and link to COVID-19: A comprehensive review of the reported associations and their possible underlying mechanisms

Microbial Pathogenesis, Journal Year: 2022, Volume and Issue: 169, P. 105658 - 105658

Published: June 25, 2022

Language: Английский

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Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(9), P. 4088 - 4096

Published: May 11, 2022

Abstract Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions coronavirus disease‐19 (COVID‐19). Host particular those related to immune determine patients' susceptibility COVID‐19 severity pathophysiology. Gene polymorphisms such as single nucleotide (SNPs) of interferons, TNF , IL1, IL4, IL6, IL7, IL10 IL17 predispose patients form acute syndrome coronavirus‐2 (SARS‐COV‐2). These mainly alter gene expression cause a response by B cells, T monocytes, neutrophils, natural killer cells participating storm. Moreover, cytokines chemokines SNPs associated with clinical outcomes depending on corresponding effect. Additionally, encoding toll‐like receptors (TLRs) TLR3 TLR7 TLR9 have been symptoms. The specific relation these mutations novel variants concern (VOCs) remains be elucidated. Genetic within proinflammatory cytokines, receptors, TLRs disease severity. Understanding host SARS‐COV‐2 opens insights control pathophysiology emerging infections.

Language: Английский

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Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID‐19 outcomes: Genome‐wide cross trait analysis and bidirectional Mendelian randomization study

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(2)

Published: Feb. 1, 2023

Abstract Coronavirus Disease (COVID‐19) may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. Using latest data from COVID‐19 host genetics consortium consortia on RA SLE, we conducted genome‐wide cross‐trait analysis to examine shared etiology between RA/SLE evaluated causal associations using bidirectional Mendelian randomization (MR). The meta‐analysis identified 23, 28, 10 loci for severe COVID‐19, hospitalization, SARS‐CoV‐2 infection RA, 14, 17, 7 respectively. Co‐localization five variants in TYK2, IKZF3, PSORS1C1 , COG6 four CRHR1, FUT2 NXPE3 involved function, angiogenesis coagulation. Bidirectional MR suggested associated higher risk not related or SLE. Our novel findings improved understanding by an increased hospitalization people liability RA.

Language: Английский

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Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 12, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious virus that the cause of disease 2019 (COVID-19) pandemic which has posed serious threat to public health. COVID-19 characterized by wide spectrum clinical manifestations, ranging from asymptomatic infection mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms assemble in response danger microbial signals. Upon activation, inflammasomes mediate innate immune defense favoring release proinflammatory cytokines and triggering pyroptotic cell Nevertheless, abnormalities inflammasome functioning can result variety human diseases such as autoimmune disorders cancer. A growing body evidence showed SARS-CoV-2 induce assembly. Dysregulated activation consequent cytokine burst have been associated with severity, alluding implication pathophysiology. Accordingly, an improved understanding inflammasome-mediated inflammatory cascades essential uncover immunological mechanisms pathology identify effective therapeutic approaches for this devastating disease. In review, we summarize most recent findings on interplay between contribution activated progression. We dissect involving machinery immunopathogenesis. addition, provide overview inflammasome-targeted therapies antagonists potential utility treatment.

Language: Английский

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SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114076 - 114076

Published: April 1, 2024

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity. accumulates most mutations after infection, supporting zoonosis airway. perform head-to-head competitions highest for Gamma Delta. Under these conditions, RNA recombination favors encoding B.1.617.1 lineage 3' end. Based on growth kinetics, Alpha, Gamma, Delta exhibit increased compared D614G. In contrast, global success likely derives from transmission antigenic variation. Our data provide molecular evidence support epidemiological observations VOC

Language: Английский

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Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach

Diseases, Journal Year: 2024, Volume and Issue: 12(5), P. 95 - 95

Published: May 6, 2024

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, outcomes persistent COVID-19 symptoms in encompassing vulnerable populations, such as pregnant women oncological patients. Our objective is to emphasize critical significance adopting an integrated approach for early detection appropriate management long COVID. The incidence severity can significant impact on quality life patients course disease case pre-existing pathologies. Particularly, fragile patients, presence PASC related significantly worse survival, independent from vulnerabilities treatment. It important try achieve recognition management. Various mechanisms are implicated, resulting wide range presentations. Understanding specific factors involved crucial tailoring effective interventions support strategies. Management approaches involve biopsychosocial assessments treatment comorbidities, autonomic dysfunction, well multidisciplinary rehabilitation. overall one gradual improvement, with recovery observed majority, though not all, As research long-COVID continues evolve, ongoing studies likely shed more light intricate relationship between chronic diseases, status, cardiovascular psychiatric disorders, effects This information could guide healthcare providers, researchers, policymakers developing targeted interventions.

Language: Английский

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Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 11, 2024

Abstract Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral host factors. These findings highlighted potential genetic markers identify high-risk individuals develop target interventions reduce morbimortality. Despite its importance, factors remain largely understudied in Latin-American populations. Using case–control design custom next-generation sequencing (NGS) panel encompassing 81 variants 74 genes previously associated with COVID-19 severity long-COVID, we analyzed 56 asymptomatic or mild critical cases. In agreement previous studies, our results support association between several clinical variables, including male sex, obesity common like cough dyspnea, COVID-19. Remarkably, thirteen showed an severity. Among these variants, rs11385942 ( p < 0.01; OR = 10.88; 95% CI 1.36–86.51) located LZTFL1 gene, rs35775079 0.02; 8.53; 1.05–69.45) CCR3 strongest associations. Various respiratory systemic symptoms, along rs8178521 variant 2.51; 1.27–4.94) IL10RB were presence long-COVID. The predictive model comparison mixed model, which incorporates non-genetic outperforms models. To knowledge, this first study Colombia Latin-America proposing for long-COVID based on genomic analysis. Our highlights usefulness approaches studying risk specific methodology used allowed us validate Finally, integrated illustrates importance considering precision medicine infectious diseases.

Language: Английский

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The association of APOE genotype with COVID-19 disease severity

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 5, 2022

Abstract COVID-19 has caused the recent pandemic of respiratory infection, which threatened global health. The severity symptoms varies among affected individuals, from asymptotic or mild signs to severe critical illness. Genetic predisposition explains variation in disease patients who suffer without any known background risk factors. present study was performed show association between APOE genotype and disease. 201 (101 with asymptomatic form as control group 100 illness factors case group) were detected via multiplex tetra-primer ARMS-PCR method. Results showed that e4 allele increased infection more than five times e4/e4 a 17-fold increase In conclusion, since our design based on exclusion underlying diseases predisposing related gene population, results is independently associated However, further studies are needed confirm these findings other nations demonstrate mechanisms behind role alleles severity.

Language: Английский

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