Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections DOI Creative Commons
Emily Lydon, Christina Osborne, Brandie D. Wagner

et al.

mSystems, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

ABSTRACT Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses severe pediatric vLRTI both the airway systemic circulation. To address this gap, gain insights into pathophysiology, test novel diagnostic approach, we assayed 1,305 proteins tracheal aspirate (TA) plasma from 62 critically ill using SomaScan. We performed differential expression (DE) pathway analyses comparing ( n = 40) controls with non-infectious acute failure 22), developed classifier LASSO regression, analyzed matched TA samples. further investigated impact viral load bacterial coinfection on proteome. The signature was characterized by 200 DE (P adj <0.05) upregulation interferons T cell downregulation inflammation-modulating including FABP MIP-5. A nine-protein achieved an area under receiver operator curve (AUC) 0.96 (95% CI: 0.90–1.00) for identifying vLRTI. In plasma, response more muted 56 proteins. Correlation between limited, although ISG15 elevated compartments. coinfection, observed increases TNF-stimulated protein TSG-6, as well CRP, interferon-related correlated positively interferon signaling negatively neutrophil-activation pathways. Taken together, our study provides fresh proteome identifies biomarkers potential. IMPORTANCE describe first proteomic profiling blood (vLRTI). From (TA), defined increased decreased involved modulation Using machine learning, parsimonious that distinguished high accuracy. Comparative analysis paired specimens demonstrated limited concordance, interferon-stimulated significantly upregulated identified TSG-6 CRP bacterial-viral positive correlation negative neutrophil activation new

Language: Английский

Plasma Proteins Associated with the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet and Incident Dementia DOI
Jiaqi Yang, Lauren Bernard,

Jingsha Chen

et al.

Journal of Nutrition, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Framework for precision medicine in focal segmental glomerulosclerosis: Translation of sparsentan-responsive genes in a rat model to kidney disease associated proteins in biofluids DOI
Sean Eddy, Viji Nair,

John R. Hartman

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Sparsentan, a dual endothelin receptor A inhibitor and angiotensin blocker, reduced proteinuria in patients with focal segmental glomerulosclerosis (FSGS) Phase II III studies. However, the estimated glomerular filtration rate (eGFR) endpoint was not achieved, partially attributed to disease heterogeneity among participants. Sparsentan reversed molecular fingerprint kidneys of an adriamycin-challenged rat model chronic kidney disease, consistent phenotypic data. Transcriptomic profiles from this were used identify differentially expressed genes, 388 which had directionality, networks responsive sparsentan. These included relevant FSGS, including suppression cytokine signaling, immune inflammatory pathways as well inhibition downstream activation. Human orthologs genes upregulated by sparsentan elevated (p<0.001) tubulointerstitial (p<0.0001) participants FSGS Nephrotic Syndrome Study Network (NEPTUNE) compared healthy living donors, pointing likely anti- action on kidneys. The gene signature both compartments negatively correlated eGFR (p<0.005) positively UPCR response profile subgroup greater severity. Several urine proteins associated score highlighting opportunities for development non-invasive surrogates enable precision medicine approach treatment antagonists. Cross-species mapping human studies identified similar subset people more severe providing basis implementing treatment.

Language: Английский

Citations

0
Prospective evaluation of plasma proteins in relation to surgical endometriosis diagnosis in the Nurses’ Health Study II DOI
Naoko Sasamoto, Long Ngo,

Allison F. Vitonis

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 115, P. 105688 - 105688

Published: April 11, 2025

Language: Английский

Citations

0
An exposome-wide assessment of 6600 SomaScan proteins with non-genetic factors in Chinese adults DOI Creative Commons
Ka Hung Chan, Jonathan Clarke, Maria Kakkoura

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract Background Proteomics offer new insights into human biology and disease aetiology. Previous studies have explored the associations of SomaScan proteins with multiple non-genetic factors, but they typically involved Europeans a limited range no evidence from East Asia populations. Methods We measured plasma levels 6,597 unique using platform in ∼2,000 participants China Kadoorie Biobank. Linear regression was used to examine cross-sectional 37 exposures across several different domains (e.g., socio-demographic, lifestyle, environmental, sample processing, reproductive clinical measurements frailty indices) concentrations specific proteins, adjusting for potential confounders testing. Findings Overall 12 were significantly associated >50 sex (n=996), age (n=982), ambient temperature (n=802) BMI (n=1035) showing largest number associations, followed by indices (n=465) RPG, SBP), not diet physical activity which showed little associations. Many these varied sex, large age-related females also menopausal status. Of examined, 43% at least one exposure, proportion higher high-abundance certain biologically-important low-abundance PSA, HBD-4) exposures. The patterns appeared generally similar those Olink proteins. Interpretation In Chinese adults an exposome-wide assessment identified health-related informing future research analytic strategies.

Language: Английский

Citations

1
Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections DOI Creative Commons
Emily Lydon, Christina Osborne, Brandie D. Wagner

et al.

mSystems, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

ABSTRACT Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses severe pediatric vLRTI both the airway systemic circulation. To address this gap, gain insights into pathophysiology, test novel diagnostic approach, we assayed 1,305 proteins tracheal aspirate (TA) plasma from 62 critically ill using SomaScan. We performed differential expression (DE) pathway analyses comparing ( n = 40) controls with non-infectious acute failure 22), developed classifier LASSO regression, analyzed matched TA samples. further investigated impact viral load bacterial coinfection on proteome. The signature was characterized by 200 DE (P adj <0.05) upregulation interferons T cell downregulation inflammation-modulating including FABP MIP-5. A nine-protein achieved an area under receiver operator curve (AUC) 0.96 (95% CI: 0.90–1.00) for identifying vLRTI. In plasma, response more muted 56 proteins. Correlation between limited, although ISG15 elevated compartments. coinfection, observed increases TNF-stimulated protein TSG-6, as well CRP, interferon-related correlated positively interferon signaling negatively neutrophil-activation pathways. Taken together, our study provides fresh proteome identifies biomarkers potential. IMPORTANCE describe first proteomic profiling blood (vLRTI). From (TA), defined increased decreased involved modulation Using machine learning, parsimonious that distinguished high accuracy. Comparative analysis paired specimens demonstrated limited concordance, interferon-stimulated significantly upregulated identified TSG-6 CRP bacterial-viral positive correlation negative neutrophil activation new

Language: Английский

Citations

0