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Immport Dataset Available (140)
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Carrillo FAB, Ojeda S, Sanchez N, Plazaola M, Collado D, Miranda T, Saborio S, Mercado BL, Monterrey JC, Arguello S, Campredon L, Chu Z, Carlson CJ, Gordon A, Balmaseda A, Kuan G, Harris E
The Lancet. Child & adolescent health
2025-09-01
PMID: 40774783
Adolescent
Chikungunya Fever
Child
Child, Preschool
Dengue
Female
HIPC 2 (2015)
Humans
Male
Nicaragua
Prospective Studies
Zika Virus Infection
Abstract:
[{'@Label': 'BACKGROUND', '@NlmCategory': 'BACKGROUND', '#text': 'Dengue, chikungunya, and Zika are diseases of major human concern. Differential diagnosis of these three diseases is complicated in children and adolescents due to overlapping clinical features (signs, symptoms, and complete blood count results). Few studies have directly compared these three diseases. We aimed to use 18 years of primary care observations from a paediatric cohort to characterise the distinguishing features of dengue, chikungunya, and Zika.'}, {'@Label': 'METHODS', '@NlmCategory': 'METHODS', '#text': 'This single-centre prospective cohort study was based on the ongoing Pediatric Dengue Cohort Study (PDCS), which started on Aug 30, 2004, in District II of Managua, Nicaragua. The PDCS was initiated to study dengue virus infections in children who attended the Health Center Sócrates Flores Vivas (HCSFV) for their medical needs; over the years, the PDCS expanded the age range (2 to <10 years expanded to 2 to <18 years). The PDCS also expanded eligibility criteria to include chikungunya virus and Zika virus before they entered the geographical study area in August, 2014 and January, 2016, respectively. For this study, we included laboratory confirmed cases of dengue, chikungunya, and Zika enrolled in the PDCS between Jan 19, 2006, and Dec 31, 2023, and evaluated at the HCSFV. We assessed clinical features (clinical records and laboratory results) during the first 10 days of illness using generalised additive models, day-specific and disease-specific prevalence estimates, and machine learning models.'}, {'@Label': 'FINDINGS', '@NlmCategory': 'RESULTS', '#text': 'We characterised 1405 dengue, 517 chikungunya, and 522 Zika cases. The median age was 10·0 years (IQR 7·0-12·7); 1165 (47·7%) cases were male and 1279 (52·3%) were female. The prevalence of many clinical features shown by dengue, chikungunya, and Zika cases differed substantially overall, by age, and by day of illness. The presence of basophilia (prevalence difference 42·3% [95% CI 37·4 to 47·0]), monocytopenia (13·0% [10·0 to 16·4]), abdominal pain (19·1% [15·7 to 22·9]), and leukopenia (41·1% [36·2 to 45·6]) best distinguished dengue; the presence of arthralgia (60·5% [56·3 to 64·2]) and absence of papular rash (-14·9% [-17·2 to -12·7]), leukopenia (-32·0% [-36·7 to -27·1]), and conjunctival injection (-4·9% [-6·6 to -3·3]) best distinguished chikungunya; and the presence of generalised rash (35·0% [30·1 to 39·7]) and absence of fever (-37·3% [-41·7 to -33·0]), headache (-36·2% [-41·1 to -31·2]), myalgia (-30·1% [-33·9 to -26·2]), and lymphocytopenia (-41·9% [-46·6 to -37·1]) best distinguished Zika. Dengue and chikungunya cases showed similar temperature dynamics during acute illness, and their mean temperatures were higher than Zika cases. 62 laboratory confirmed afebrile dengue cases, which would not be captured by any widely used international case definition, presented most similarly to afebrile Zika cases, but five (8·1%) had warning signs of dengue disease severity. Based on boosted regression tree models, the presence of arthralgia and absence of basophilia and leukopenia most distinguished chikungunya, the presence of basophilia and leukopenia most distinguished dengue, and the absence of fever most distinguished Zika.'}, {'@Label': 'INTERPRETATIONS', '@NlmCategory': 'CONCLUSIONS', '#text': 'These findings substantially update the understanding of dengue, chikungunya, and Zika in a paediatric population and identify various clinical features that could improve differential diagnoses. The occurrence of afebrile dengue warrants reconsideration of current guidance.'}, {'@Label': 'FUNDING', '@NlmCategory': 'BACKGROUND', '#text': 'US National Institutes of Health.'}, {'@Label': 'TRANSLATION', '@NlmCategory': 'UNASSIGNED', '#text': 'For the Spanish translation of the abstract see Supplementary Materials section.'}]
Wells SB, Rainbow DB, Mark M, Szabo PA, Ergen C, Caron DP, Maceiras AR, Rahmani E, Benuck E, Valiollah Pour Amiri V, Chen D, Wagner A, Howlett SK, Jarvis LB, Ellis KL, Kubota M, Matsumoto R, Mahbubani K, Saeb-Parsy K, Conde CD, Richardson L, Xu C, Li S, Mamanova L, Bolt L, ...
Nature immunology
2025-08-13
PMID: 40804529
Columbia University
HIPC 2 (2015)
HIPC 3 (2022)
Abstract:
The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.
Pickering H, Alipanah-Lechner N, Chen E, Duchen D, Maecker HT, Kim-Schulze S, Montgomery RR, Cotsapas C, Steen H, Krammer F, Langelier CR, Levy O, Baden LR, Melamed E, Ehrlich LI, McComsey GA, Sekaly RP, Cairns CB, Haddad EK, Shaw AC, Hafler DA, Corry DB, Kheradmand F, Atkinson MA, Brakenridge SC, ...
JCI insight
2025-08-08
PMID: 40608426
Acute Lung Injury
Adult
Aged
Alleles
COVID-19
Female
HIPC 1 (2010)
HIPC 2 (2015)
HIPC 3 (2022)
Histocompatibility Antigens Class I
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Respiration, Artificial
SARS-CoV-2
Yale University
Abstract:
MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower airway. We identified 560 major allele homozygous patients, and 426 and 50 with 1 or 2 copies of the variant allele, respectively. MICBG406A conferred reduced odds of severe COVID-19. MICBG406A homozygous participants demonstrated 34% reduced cumulative odds for mechanical ventilation or death and 43% reduced risk for mortality. Patients with MICBG406A variant alleles had reduced soluble inflammatory mediators and differential regulation of multiple immune pathways. These findings demonstrate a potentially novel association between increasing MICBG406A variant allele copies and reduced COVID-19 severity, independent of SARS-CoV-2 viral burden and humoral immunity, suggesting the NKG2D-ligand pathway as an intervention target.
Tsuji I, Dominguez D, Hernandez J, Kpamegan E, Zambrana JV, Balmaseda A, Dean H, Sharma M, Harris E
The Journal of infectious diseases
2025-07-30
PMID: 40179248
Adolescent
Antibodies, Viral
Antibody Affinity
Child
Child, Preschool
Cohort Studies
Dengue
Dengue Virus
Female
HIPC 2 (2015)
Humans
Male
Nicaragua
Abstract:
Antibody avidity is indicative of antibody affinity maturation following virus infection or vaccination. To determine correlation between preexisting anti-dengue virus (DENV) antibody avidity and secondary DENV exposure outcomes, we assessed anti-DENV antibody avidity, represented as avidity index (antibody response/dissociation rate) in sera of Nicaraguan Pediatric Dengue Cohort Study participants prior to symptomatic or inapparent secondary DENV infections. The avidity index was significantly higher in participants who subsequently developed inapparent versus symptomatic infections. Risk factor analysis suggested that odds of inapparent DENV infection increase as avidity index increases. Antibody avidity index is an important parameter for characterizing protective DENV immune responses.
Kollmann TR, Amenyogbe N, Schaltz-Buchholzer F, Bæk O, Campbell J, Lynn DJ, Campbell AJ, Aaby P, Stabell Benn C, Netea MG, Divangahi M
The Journal of infectious diseases
2025-07-11
PMID: 39913242
Animals
Bacteremia
BCG Vaccine
HIPC 2 (2015)
Humans
Infant, Newborn
Mycobacterium tuberculosis
Tuberculosis
Vaccination
Abstract:
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is a leading cause of death. BCG is the only licensed TB vaccine. Preclinical studies have shown that in adults, intravenous administration of BCG improves protection against TB. We hypothesize that intradermal administration of BCG to the human newborn leads to low-grade BCG bacteremia and that this systemic dissemination improves protection against Mtb infection. This hypothesis is based on supporting observations including animal and human studies. It is a testable hypothesis and offers to deliver immediately actionable insight to advance the global efforts against TB.
Qualls AE, Tsao T, Lui I, Lim SA, Su Y, Chen E, Duchen D, Maecker HT, Kim-Schulze S, Montgomery RR, Krammer F, Langelier CR, Levy O, Baden LR, Melamed E, Ehrlich LI, McComsey GA, Sekaly RP, Cairns CB, Haddad EK, Shaw AC, Hafler DA, Corry DB, Kheradmand F, Atkinson MA, ...
JCI insight
2025-07-08
PMID: 40402577
Adult
Aged
Alleles
Antibody-Dependent Cell Cytotoxicity
COVID-19
Female
Genetic Predisposition to Disease
HIPC 1 (2010)
HIPC 2 (2015)
HIPC 3 (2022)
Humans
Killer Cells, Natural
Male
Middle Aged
Polymorphism, Genetic
Receptors, IgG
SARS-CoV-2
Severity of Illness Index
Viral Load
Yale University
Abstract:
CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 cohort (IMPACC), a comprehensive longitudinal dataset with extensive transcriptomic, proteomic, and clinical data. The high-affinity CD16AV176 allele was associated with a significantly reduced risk of ICU admission, mechanical ventilation, and severe disease trajectories. Lower anti-SARS-CoV-2 IgG titers were correlated to CD16AV176; however, there was no difference in viral load across CD16A genotypes. Proteomic analysis revealed that participants homozygous for CD16AV176 had lower levels of inflammatory mediators. These findings suggest that CD16AV176 enhances early NK cell-mediated immune responses, limiting severe respiratory complications in COVID-19. This study identifies a protective genetic factor against severe COVID-19, informing future host-directed therapeutic strategies.
Smith D, Eichinger A, Fennell É, Xu-Monette ZY, Rech A, Wang J, Esteva E, Seyedian A, Yang X, Zhang M, Martinez D, Tan K, Luo M, Young KJ, Murray PG, Park C, Reizis B, Pillai V
Nature communications
2025-07-01
PMID: 40593805
Adult
Aged
B-Lymphocytes
Castleman Disease
Cell Differentiation
Chemokine CXCL13
Columbia University
Cytokines
Dendritic Cells, Follicular
Female
HIPC 2 (2015)
HIPC 3 (2022)
Humans
Interleukin-6
Lymph Nodes
Lymphocyte Activation
Male
Middle Aged
Signal Transduction
Single-Cell Analysis
Stromal Cells
Transcriptome
Vascular Endothelial Growth Factor A
Abstract:
To determine the cellular and molecular basis of Castleman Disease (CD), we analyze the spatial proteome and transcriptome from a discovery (n = 9 cases) and validation (n = 13 cases) cohort of Unicentric CD, idiopathic Multicentric CD, HHV8-associated MCD, and reactive lymph nodes. CD shows increased stromal cells that form unique microenvironments. Interaction of activated follicular dendritic cell (FDC) cytoplasmic meshworks with mantle-zone B cells is associated with B-cell activation and differentiation. CXCL13+ FDCs, PDGFRA + T-zone reticular cells (TRC), and ACTA2-positive perivascular reticular cells (PRC) were the predominant source of increased VEGF expression and IL-6 signaling. MCD is characterized by increased TRC while UCD shows increased B-reticular cells (BRC). VEGF expression by FDCs is associated with peri-follicular neovascularization. FDC, TRC and PRC of CD activates JAK-STAT, TGFβ, and MAPK pathways via specific ligand-receptor interactions. Here, we show that stromal-cell activation and associated B cell activation and differentiation, neovascularization and stromal remodeling underlie CD.
Tsai W-Y, Tseng AC, Chen G-H, Hsieh S-C, Balmaseda A, Nerurkar VR, Harris E, Wang W-K
Microbiology spectrum
2025-07-01
PMID: 40401969
Antibodies, Viral
Child
Child, Preschool
Female
HIPC 2 (2015)
Humans
Infant
Male
Nicaragua
Viral Envelope Proteins
West Nile Fever
West Nile virus
Zika Virus
Zika Virus Infection
Abstract:
[{'@Label': 'UNLABELLED', '#text': 'Since its introduction to the Western Hemisphere in 1999 in New York City, West Nile virus (WNV) has spread throughout the continental USA and moved into Canada, Mexico, Caribbean, and Central and South Americas. While WNV has caused ~7 million human infections and >59,000 cases in the USA and >6,000 cases in Canada, only few human cases have been reported in Latin America. Due to the cross-reactivity of anti-envelope antibodies, the detection of WNV infection by serology to explore its epidemiology in Latin America, where multiple flaviviruses co-circulate, remains a challenge. Previously, we reported that anti-premembrane (prM) antibodies can distinguish between four flavivirus (WNV, dengue, Zika, and yellow fever viruses) infections. In this study, we examined 73 samples from 40 Zika cases from a pediatric cohort in Nicaragua using Western blot analysis and detected anti-prM antibodies to WNV in three participants in samples collected between 2016 and 2017, suggesting previous WNV infection prior to ZIKV infection. Analysis of available archived samples revealed anti-WNV prM antibodies in the earliest samples (2007-2009), which were further confirmed by plaque reduction neutralization test, suggesting that they were infected by WNV prior to 2007-2009. Our report of WNV infection in three Nicaraguan children, corresponding to a seropositive rate of 7.5%, highlights the transmission of WNV in humans in Central America prior to 2007. Future studies with improved serological tests for WNV surveillance in Latin America are needed to enhance our understanding of the epidemiology and transmission of WNV in the Western Hemisphere.'}, {'@Label': 'IMPORTANCE', '@NlmCategory': 'OBJECTIVE', '#text': 'Since its arrival to North America in 1999, West Nile virus (WNV) has caused multiple outbreaks in birds and humans, with thousands of human cases in the USA and Canada, whereas in Latin America, WNV has mainly been detected in birds and horses with few human cases. Due to cross-reactivity of anti-envelope antibodies among different flaviviruses, detection of WNV infection by serology to explore its epidemiology in Latin America remains a challenge. Previously, we reported that anti-premembrane antibodies can discriminate four flavivirus infections using Western blot analysis. Based on anti-WNV premembrane antibodies and confirmation by neutralization test, we report three Nicaraguan children with WNV infection, corresponding to a seropositive rate of 7.5%. Our findings underscore the transmission of WNV in humans in Central America and the application of improved seroepidemiological tools to address the knowledge gaps on the prevalence and distribution of WNV in Latin America and the Western Hemisphere.'}]
Zheng Y, Caron DP, Kim JY, Jun SH, Tian Y, Mair F, Stuart KD, Sims PA, Gottardo R
Nature communications
2025-07-01
PMID: 40595741
Antibodies
Columbia University
COVID-19
Epitopes
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
HIPC 2 (2015)
HIPC 3 (2022)
Humans
Membrane Proteins
Seattle Children's Research Institute
Single-Cell Analysis
Transcriptome
Abstract:
Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm, a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations with negative- and positive-expression of surface protein markers across 13 public datasets, effectively removing technical variation across batches and improving cell-type separation. ADTnorm enables efficient integration of public CITE-seq datasets, each with unique experimental designs, paving the way for atlas-level analyses. Beyond normalization, ADTnorm includes built-in utilities to aid in automated threshold-gating as well as assessment of antibody staining quality for titration optimization and antibody panel selection. Applying ADTnorm to an antibody titration study, a published COVID-19 CITE-seq dataset, and a human hematopoietic progenitors study allowed for identifying previously undetected phenotype-associated markers, illustrating a broad utility in biological applications.
Grabauskas T, Verschoor CP, Trinity L, Marches R, Thibodeau A, Nehar-Belaid D, Eryilmaz G, Picard E, Kuo CL, Schmader KE, Colon-Emeric C, Whitson HE, Paust S, García-Sastre A, Banchereau J, Kuchel GA, Ucar D
bioRxiv : the preprint server for biology
2025-06-27
PMID: 40666903
HIPC 3 (2022)
Icahn School of Medicine at Mount Sinai
Abstract:
Cytomegalovirus (CMV), a common herpesvirus, establishes lifelong latency and increases in prevalence with age; yet its systemic impact on the aging immune system remains incompletely understood. We profiled circulating immune cells from healthy older adults (median age: 73) who were CMV(+) or CMV(-) using single-cell RNA-sequencing and validated key findings by flow cytometry. CMV(+) individuals exhibited significant expansion of adaptive immune cells: CD4+ and CD8+ TEMRA T, GZMK+ CD8+ T, γδ T, and atypical B cells. Among innate immune cells, monocytes and dendritic cells remained largely unchanged while KLRC2 + (adaptive) NK cells increased and CD56dim NK cells decreased. To facilitate CMV assessment in datasets with unknown CM serostatus, we developed CMVerify, a machine learning classifier that accurately predicts CMV serostatus from single-cell data across platforms and age groups (97% accuracy). These findings reveal extensive CMV-associated immune remodeling in older adults and underscore the importance of incorporating CMV status in studies of immune aging.
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