MicroRNAs Biomarkers and Host Response Pathways in Severe Pulmonary Hemorrhagic Syndrome due to Leptospirosis
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ABSTRACT:
PROVIDER: PRJNA1195885 | ENA |
REPOSITORIES: ENA
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Project description:Serum microRNA profiling revealed distinct expression patterns between the two phenotypes. From the top 81 significantly expressed microRNAs, seven were selected for validation. Among these, miR-5010-3p and miR-147b-3p had area under the curve (AUC) values of 0.72 (95% CI: 0.62–0.81) and 0.66 (95% CI: 0.55–0.76) for discriminating SPHS. Notably, the two microRNAs could detect SPHS in patients who were yet to manifest chest radiograph shadows at the time of sample collection, with consistent AUC values.
2025-04-09 | GSE283845 | GEO
Project description:Background: Leptospirosis is a global zoonotic infectious disease with various clinical manifestations ranging from mild self-limiting illness to life-threatening infection with multi-organ damage. This study was aimed at investigating transcription profiles from whole blood samples of patients with leptospirosis and identifying genes as novel biomarkers for predicting severe leptospirosis. Methods: In a discovery cohort, 12 serum samples of patients with severe and non-severe leptospirosis at initial clinical presentation were selected for gene expression profiling using the NanoString nCounter PanCancer IO 360 gene expression panel. In a validated cohort of 99 samples, top candidate genes were selected and further tested by qRT-PCR in whole blood samples of 30 and 69 individuals with severe and non-severe leptospirosis, respectively. Results: The discovery set identified 20 differentially expressed genes (DEGs) among the two groups. The top three down-regulated candidate genes including programmed cell death 1 (PDCD1), interleukin 4 (IL4), and nitric oxide synthase 2 (NOS2) were selected and further validated. In the validated cohort, PDCD1 levels were significantly lower in the severe group compared with the non-severe group(Stats?). Based on the ROC analysis, PDCD1 levels could discriminate between the severe and non-severe groups. Additionally , PDCD1 levels displayed good predictive power of subsequent pulmonary hemorrhage with an AUROC of 0.86 (95% CI;0.76-0.96, p = 0.007). PDCD1 also emerged as an independent prognostic factor of severe leptospirosis in the multivariate regression analysis.. Conclusion: Our data indicated that whole blood gene expression profiles were significantly different between the severe and non-severe leptospirosis groups. PDCD1 expression levels at presentation could potentially serve as a biomarker for predicting severe leptospirosis.
2025-04-01 | GSE200188 | GEO
Project description:Leptospirosis is zoonotic disease of global importance, with over a million cases andnearly 60,000 deaths annually. Symptomatic disease presentation ranges from a mildfebrile disease with non-specific symptoms to severe forms, characterized by multi-organ failure, lung hemorrhage, and death. Factors governing severe outcomes remainunclear, but the host immune response likely plays an important role. In the presentstudy, we applied high throughput techniques to identify the antibody profiles ofpatients with severe and mild leptospirosis. We discovered a limited number ofimmunodominant antigens, specific to patients. Surprisingly, we found the antibodyrepertoire varies in patients with different clinical outcomes and hypothesized thatpatients with mild symptoms were protected from severe disease due to pre-existingantibodies, while the profile of patients with severe outcomes was representative of afirst exposure. These findings represent a substantial step forward in the knowledge ofthe humoral immune response to Leptospira infection, and we have identified newtargets for vaccine and diagnostic test development.
2016-09-10 | GSE86630 | GEO
Project description:Background: Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. Methods: In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. Results: The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. Conclusion: Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.
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2011-01-24 | E-GEOD-26697 | biostudies-arrayexpress
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2016-09-23 | GSE72946 | GEO
Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures. Microarrays were performed on liver and spleen samples from mice collected at days 1, 3, and 5 post-infection with mouse adapted Zaire ebolavirus or from time-matched mock-infected animals.
2014-05-01 | E-GEOD-57214 | biostudies-arrayexpress
Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures.
2014-05-01 | GSE57214 | GEO
Project description:Gene expression profiling of whole blood in patients with severe leptospirosis
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