Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts

The American Journal of Human Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Impact of FcRn antagonism on vaccine-induced protective immune responses against viral challenge in COVID-19 and influenza mouse vaccination models

Human Vaccines & Immunotherapeutics, Год журнала: 2025, Номер 21(1)

Опубликована: Март 3, 2025

Antagonism of the neonatal Fc receptor through an engineered antibody fragment, such as efgartigimod, results in a decrease immunoglobulin G levels. This approach is being evaluated therapeutic strategy for treatment IgG-mediated autoimmune diseases. Our goal was to evaluate impact mFc-ABDEG, mouse-adapted fragment with mode action highly similar on vaccine-induced protective immune responses against viral infections. Therefore, mouse vaccination models COVID-19 and influenza were employed, utilizing mRNA vaccine (COMIRNATY) adjuvanted, inactivated quadrivalent (Seqirus+AddaVax), respectively. In both models, induced robust humoral responses. As expected, animals treated mFc-ABDEG had lower levels virus-specific IgG, while IgM remained unaffected. The strong Th1-type T cell response irrespective treatment. Influenza resulted poor induction, regardless treatment, due Th2-biased that vaccines typically induce. Importantly, no effect immunity live challenges models. Vaccinated equally protected non-treated vaccinated controls. These non-clinical data demonstrate FcRn antagonism did not affect generation cellular responses, or protection challenges. substantiate clinical observations that, although IgG titers reduced, efgartigimod impair ability generate new specific timing vaccination.

Язык: Английский

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Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai

Journal of Clinical Immunology, Год журнала: 2024, Номер 44(3)

Опубликована: Март 10, 2024

Abstract Objective We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during Omicron variant wave SARS-CoV-2. Methods Type interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity for vitro interference with antiviral activity IFN was assessed by SARS-CoV-2 replicon system. An analysis demographic profiles patients exhibiting also conducted. Results In this cohort, 11.8% severe/critical cases exhibited existence IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, an elderly male patient tendency. Notably, these exerted pronounced inhibitory effect on against under controlled conditions. Furthermore, noteworthy correlation discerned between presence critical parameters, including C-reactive protein (CRP) levels, D-dimer lymphocyte counts. Conclusion is pervasive risk factor COVID-19 population.

Язык: Английский

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Risk factors for bloodstream infection in COVID-19 patients in intensive care units: a systematic review and meta-analysis

BMC Infectious Diseases, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 3, 2025

Abstract Background Risk factors for bloodstream infection in patients with COVID-19 the intensive care unit (ICU) remain unclear. The purpose of this systematic review was to study risk BSI admitted ICUs COVID-19. Methods A search performed on PubMed, EMBASE, Cochrane Library, and Web Science up July 2024. Data were reported as combined odds ratio (OR) categorical variables weighted mean difference (WMD) continuous variables. Results 6914 studies retrieved, which 55 included meta-analysis. Men (OR = 1.28, 95% CI: 1.10–1.50, P 0.006), high SAPS II score (WMD 6.43, 0.23–12.63, 0.042), diabetes 1.34, 1.04–1.73, 0.022), tracheal intubation 8.68, 4.68–16.08, < 0.001), mechanical ventilation 22.00, 3.77-128.328, ECMO 2.70, 1.17–6.26, 0.020), central venous cannulation 9.33, 3.06–28.43, prolonged ICU stay 10.37, 9.29–11.44, methylprednisolone use 2.24, 1.24–4.04, 0.008), combination Tocilizumab 4.54, 1.09–18.88, 0.037) ICU-BSI patients. Conclusion We identified 10 In future studies, these can be establish a more comprehensive accurate prediction model Targeted measures taken earlier control BSI.

Язык: Английский

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Investigating the relationship between the immune response and the severity of COVID-19: a large-cohort retrospective study

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

The COVID-19 pandemic has left an indelible mark globally, presenting numerous challenges to public health. This crisis, while disruptive and impactful, provided a unique opportunity gather precious clinical data extensively. In this observational, case-control study, we utilized collected at the Azienda Sanitaria Universitaria Friuli Centrale, Italy, comprehensively characterize immuno-inflammatory features in patients. Specifically, employed multicolor flow cytometry, cytokine assays, inflammatory biomarkers elucidate interplay between infectious agent host's immune status. We characterized profiles within first 72 hours of hospital admission, stratified by age, disease severity, time elapsed since symptom onset. Our findings indicate that patients admitted shortly after onset exhibit distinct pattern compared those who arrive later, more active response heightened activity, but lower markers tissue damage. used univariate multivariate logistic regression models identify informative for outcome severity. Predictors incorporating significantly outperformed standard baselines, identifying up 59% with positive outcomes maintaining false omission rate as low 4%. Overall, our study sheds light on aspects observed prior vaccination, providing insights guiding management first-time infections novel virus.

Язык: Английский

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The rational use of glucocorticoids may reduce the risk of readmission in menopausal women with knee osteoarthritis: results from a five-year longitudinal study

Arthritis Research & Therapy, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 6, 2025

To investigate the effect of glucocorticoids (GCs) on risk readmission in menopausal women with knee osteoarthritis (OA). The study cohort comprised 80 OA treated at a tertiary hospital affiliated Shanxi Medical University and who underwent follow-up between September 2018 2023. Then collected longitudinal monitoring data were used to construct semi-variable coefficient shared Gamma frailty model (VCSGF). Based results this model, we explored impact GCs made predictions. mean patient age entry was 64.7 ± 9.3 (range 50–82 years). And during research, patients admitted 2.4 1.8 times 1–11 times). Compared have not drug, early reduced by 96% (HR = 0.04, 95%CI: 0.006 ~ 0.284, $$\:P<0.001$$ ). This protective diminished over time ( $$\:{\gamma\:}_{2l}\left({t}_{0}\right)=0.629,P<0.001$$ In addition, admission recurrent symptoms roughly 3.35-fold higher drink alcohol than do (95%CI: 1.661~6.794, GC use OA, although time. Therefore, without further contraindications, may be moderation reduce risk. clinical practice, additional research is needed timing appropriate treatment develop more rational program for use.

Язык: Английский

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Glucocorticoids as emerging pollutants in surface water: A systematic review on their global occurrence and distribution

Environmental Research, Год журнала: 2025, Номер 273, С. 121280 - 121280

Опубликована: Март 1, 2025

Язык: Английский

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Annexin A1/FPR2 pathway modulates leukocyte function during Escherichia coli‐induced pneumonia to promote resolution of inflammation and restores lung function

British Journal of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Gram-negative bacteria are the main causes of pneumonia in nosocomial environment. Inflammation triggered during is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage dissemination. Emerging data shows that annexin A1 (ANXA1) signalling through its receptor FPR2 promotes host resistance resilience preclinical models infectious disease. Using a mouse model Escherichia coli-induced pneumonia, role ANXA1/FPR2 on key steps inflammation resolution was evaluated. Anxa1 Fpr2/3 knockout mice, intranasally infected with E. coli, exhibited exacerbated neutrophilic inflammation, higher dissemination, decreased neutrophil apoptosis/efferocytosis counts airways levels inflammatory cytokines/chemokines coupled marked lung dysfunction, as compared WT mice. Treatment WT-infected mice ANXA1 peptidomimetic, I-(2-26), increased neutrophils improved lungs, resulting an improvement function. The pan-caspase inhibitor Z-VAD-FMK prevented I-(2-26)-induced underlining apoptosis mechanism I-(2-26) promotion coli pneumonia. In addition, treatment numbers airway macrophages promoted macrophage phagocytosis vitro. summary, these findings highlight pathway nonredundant demonstrate potential host-directed therapeutic approach treat diseases.

Язык: Английский

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Glucocorticoid-Mediated Extracellular Matrix Regulation: Implications for Precision Therapy

Biomedicines, Год журнала: 2025, Номер 13(6), С. 1282 - 1282

Опубликована: Май 23, 2025

Glucocorticoids (GCs) have revolutionized the treatment of multidisciplinary diseases. Recently, its role in severe infectious diseases has been revisited and discussed since COVID-19 pandemic. Previous research discussions focused more on their anti-inflammatory effects impact immune system, with limited study other aspects action mechanisms. In recent years, it discovered that glucocorticoids can regulate extracellular matrix by influencing cellular microenvironment processes such as fibrosis, thereby exerting regulatory This article summarizes current GC-mediated (ECM) remodeling. It emphasizes dual ECM a therapeutic target source biomarkers, identifies molecular mechanisms potential biomarkers for precise glucocorticoid therapy, type I collagen (PRO-C1), III (PRO-C3), fibrillin-C (FBN-C), degradation (C3M). These findings may also contribute to development new drugs.

Язык: Английский

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Safety and efficacy of glucocorticoids in the treatment of COVID-19: A meta-analysis of randomized control trials

Expert Review of Respiratory Medicine, Год журнала: 2023, Номер 17(1), С. 81 - 96

Опубликована: Янв. 2, 2023

Background It is unclear the efficacy and safety of glucocorticoids compared with placebo or usual care for treatment COVID-19.

Язык: Английский

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