Gene expression profiling of whole blood in patients with severe leptospirosis
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PROVIDER: PRJNA823595 | ENA |
REPOSITORIES: ENA
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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:Whole blood transcriptional profiling of Brazilian patients with acute leptospirosis to identify mechanisms associated with case fatality
2016-09-23 | GSE72946 | 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.
2021-07-07 | GSE179426 | GEO
Project description:The identification of COVID-19 patients with high-risk of severe disease is a challenge in routine care. We performed blood RNA-seq gene expression analyses in severe hospitalized patients compared to healthy donors. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
2021-05-27 | GSE171110 | GEO
Project description:Whole blood transciptome analysis in severe Covid-19 patients and healthy donors
| PRJNA718349 | ENA
Project description:Background. Leptospirosis is among the most widespread zoonoses worldwide. Severe pulmonary hemorrhagic syndrome (SPHS) represents a serious complication of leptospirosis, with poor understanding of its underlying mechanisms and an urgent need for identification of effective biomarkers. Methods. A nested case-control analysis of the blood specimens obtained from two previous multi-center cohorts was conducted. Candidate microRNAs were initially discovered through a global profiling of 800 serum microRNAs, then validated using real-time polymerase-chain reactions. We further conducted a multi-omics analysis incorporating transcriptomic and proteomic data to identify enriched pathways through which the newly identified microRNAs could regulate. Findings. A total of 28 SPHS and 140 non-SPHS patients were evaluated by serum microRNA profiling, revealing 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, and in a subgroup of patients who were recruited on day 2 of illness or earlier, with consistent AUC values. Integrated gene-protein pathway enrichment analysis revealed numerous pathways involving host immune responses. Among these, the tumor necrosis factor signaling pathway was the most significant with many of its member genes being targeted by miR-5010-3p or miR-147b-3p.
2026-02-09 | PXD052319 | Pride
Project description:Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. In this study, we sought to identify a blood gene expression biomarker correlating with 12-week response to infliximab in patients with moderate to severe disease. Response was assessed using dynamic contrast-enhanced MRI imaging of the wrist.
2014-09-01 | GSE58795 | GEO
Project description:Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis
| PRJNA743674 | ENA
Project description:Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. In this study, we sought to identify a blood gene expression biomarker correlating with 12-week response to infliximab in patients with moderate to severe disease. Response was assessed using dynamic contrast-enhanced MRI imaging of the wrist. Baseline whole blood samples from 59 patients were collected as part of a placebo-controlled clinical study of infliximab in rheumatoid arthritis. Samples were profiled by Affymetrix microarray and correlation between gene expression and 12-week response was assessed. DAS28 (Disease Activity Score including a 28-joint count)
2014-09-01 | E-GEOD-58795 | biostudies-arrayexpress