Global transcriptome analysis identifies a signature for early disseminated Lyme disease and its resolution
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145974 | GEO | 2020/04/03
REPOSITORIES: GEO
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Project description:Lyme disease is challenging to diagnose, as clinical manifestations are variable and current tools to detect nucleic acid or antibody responses from Borrelia burgdorferi infection have low sensitivity. Here we conducted the first study of the global transcriptome of patients with Lyme disease to identify potential diagnostic biomarkers. Twenty-nine patients were enrolled and compared to 13 healthy controls at three time points after infection. Fifteen publicly available transcriptome datasets from patients in vivo or infection models in vitro were used to assess specificity of differentially expressed genes (DEGs). We found that Lyme disease results in profound and sustained changes in the patient transcriptomes, with a specific signature that shares 44% DEGs with other infections. Gene expression profile from peripheral mononuclear blood cells (PBMC) of Lyme disease patients against healthy controls was undertaken. A total of 29 Lyme disease patients were sampled at 3 time points: acute Lyme pre-treatment (V1), 3 weeks later, immediately following completion of a standard course of antibiotics (V2), and 6 months following treatment completion (V5). 13 healthy controls were also sampled at one time point. Total RNA was extracted from 10e7 PBMC, followed by mRNA purification, paired-end barcode library preparation and sequencing on an Illumina Hiseq 2000.
2016-02-15 | E-GEOD-63085 | biostudies-arrayexpress
Project description:Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.
2016-07-20 | GSE84479 | GEO
Project description:Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p=0.027 and p=0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p=0.01) and the decrease correlates with chemokine levels (p=0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. A total of 65 immune and inflammatory mediators were profiled in serum samples derived from early Lyme disease patients and age- and sex-matched controls. These samples have been generated as part of a prospective cohort study that includes a well-defined cohort of patients with acute Lyme disease enrolled from a Lyme endemic area of the mid-Atlantic United States. Only patients with untreated, confirmed early Lyme disease manifesting an active EM skin lesion at the time of enrollment, as defined by CDC case criteria are eligible. Patients with a history of prior Lyme disease or the presence of confounding preexisting medical conditions associated with prolonged fatigue, pain or neurocognitive symptoms are excluded. Controls are nonhospitalized age- and sex-matched and have no prior history of Lyme disease or any exclusionary medical conditions including lack of inflammatory disorders.
2014-04-25 | E-GEOD-55815 | biostudies-arrayexpress
Project description:Lyme disease is a tickborne illness that causes an estimated 476,000 infections annually in the United States. New diagnostic tests are urgently needed, as existing antibody-based assays lack sufficient sensitivity and specificity. Using transcriptome profiling by RNA-Seq, targeted RNA sequencing, and machine learning (ML)-based classification of 218 subjects, we identified a 31-gene Lyme disease classifier (LDC) to discriminate early Lyme patients from “non-Lyme” controls infected with influenza, bacteremia, or tuberculosis or uninfected asymptomatic controls. Among the 31 classifier genes, 23 (74.2%) had previously been described in association with clinical investigations of Lyme disease patients or in vitro cell culture and rodent studies of Borrelia burgdorferi infection. Evaluation of the LDC using an independent test set of samples from 63 subjects (16 Lyme seropositive patients, 14 Lyme seronegative patients, and 33 controls) yielded an overall sensitivity of 90.0%, specificity of 100%, and accuracy of 95.2%. The LDC was positive in 85.7% of seronegative patients and persisted for ≥3 weeks in available longitudinal samples from 9 of 12 (75%) patients. These results highlight the potential clinical utility of a gene expression classifier for diagnosis of early Lyme disease.
2022-05-01 | GSE196192 | GEO
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Project description:Using RNA-seq, 39 cerebral cortex RNA samples were sequenced. The study design was as follows: Ad libitum fed rats at 6 months (n=3, 6 individuals pooled), 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Calorie restricted rats at 6 months (n=3, 6 individuals pooled), 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Rats fed alpha lipoic acid as a supplement to ad libitum at 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Diet switching groups, where diet was changes at 12 months; 28 month ad libitum switched to calorie restriction (n=3, 6 individuals pooled), 28 month calorie restriction switched to ad libitum (n=3, 6 individuals pooled), 28 month ad libitum plus lipoic acid switched to calorie restriction (n=3, 6 individuals pooled), 28 month calorie restriction switched to ad libitum plus lipoic acid (n=3, 6 individuals pooled).
2015-11-22 | GSE57110 | GEO
Project description:The survival of transplant kidneys using deceased donors (DD) is inferior to living donors (LD). In this study, we conducted a whole-transcriptome expression analysis of 24 human kidney biopsies paired 30 minutes and 3 months post-transplantation using DD and LD. The transcriptome profile was found significantly different between two time points regardless of donor types. There were 446 differentially expressed genes (DEGs) between DD and LD at 30 minutes and 146 DEGs at 3 months, with 25 genes common to both time points. These DEGs reflected donor injury and acute immune responses associated with inflammation and cell death as early as at 30 minutes, which could be a precious window of potential intervention. DEGs at 3 months mainly represented the changes of adaptive immunity, immunosuppressive treatment, remodeling or fibrosis via different networks and signaling pathways. The expression level of 20 DEGs involved in kidney diseases, and 10 genes found dysregulated at 30 minutes were validated by quantitative PCR (qPCR) in the 24 samples analyzed by microarray as well as in a validation cohort of 33 unpaired allograft biopsies. Their expression levels were found correlated with renal function and histology at 12 months, suggesting they could be potential biomarkers to predict kidney function. This analysis revealed that SERPINA3, SLPI and CBF is upregulated at 30 minutes in DD compared to LD, whereas FTCD and TASPN7 are up-regulated at both time points; at 3 months VCAN and TIMP1 are up-regulated, whereas FOS is decreased in both donors. Taken together, divergent transcriptomic signatures between DD and LD, and changed by the time post-transplantation, might contribute to different allograft survival of two type kidney donors. Some DEGs such as FTCD and TASPN7 could be novel biomarkers not only for timely diagnosis, but also early for precise genetic intervention at donor preservation, implantation and post-transplantation, in particular to effectively improve the quality and survival of DD.
2021-06-23 | GSE178689 | GEO
Project description:Most Lyme disease patients treated with appropriate antibiotics recover rapidly and completely, but a minority of patients develop persistent symptoms correlating with disseminated disease, a greater severity of illness at presentation, and delayed antibiotic therapy. When lingering or recurrent symptoms are associated with a functional decline and persist for greater than 6 months, patients are considered to meet clinical criteria for post-treatment Lyme disease syndrome (PTLDS), although the exact molecular mechanisms underlying this condition remain unknown. We performed longitudinal whole transcriptome sequencing of PTLDS patients' immune cells. No immune mechanism specific to PTLDS were uncovered to date.
2019-02-15 | GSE77929 | GEO
Project description:Lyme disease is a tick-borne bacterial illness that occurs in areas of North America, Europe, and Asia. Early infection typically presents as generalized symptoms with an erythema migrans (EM) skin lesion. Bacterial dissemination can result in multiple EM skin lesions or in extracutaneous manifestations such as Lyme neuroborreliosis. Metabolic biosignatures of patients with early Lyme disease can potentially provide diagnostic targets, as well as highlight metabolic pathways that contribute to pathogenesis. Sera from well-characterized patients diagnosed with either early localized Lyme disease (ELL) or early disseminated Lyme disease (EDL), plus healthy individuals (HC), from the United States were analyzed by liquid chromatography-mass spectrometry (LC-MS). Comparative analyses were performed between ELL, or EDL, or ELL combined with EDL, and the HC to develop biosignatures present in early Lyme disease. A direct comparison between ELL and EDL was also performed to develop a biosignature for stages of early Lyme disease. Metabolic pathway analysis and chemical identification of metabolites with LC-tandem mass spectrometry (LC-MS/MS) demonstrated alterations of eicosanoid, bile acid, sphingolipid, glycerophospholipid, and acylcarnitine metabolic pathways during early Lyme disease . These metabolic alterations were confirmed using a separate set of serum samples for validation. The findings demonstrated the metabolic pathways altered in the host during early Lyme disease and provide evidence that the diversity in the type of early Lyme disease manifestations may be associated with particular metabolic alterations.
2019-07-02 | ST001223 | MetabolomicsWorkbench
Project description:Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p=0.027 and p=0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p=0.01) and the decrease correlates with chemokine levels (p=0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.
2014-04-25 | GSE55815 | GEO