Symptom characterization, immunobiology, and functional impact of post-Lyme disease syndrome (PTLDS)
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PROVIDER: PRJNA802951 | ENA |
REPOSITORIES: ENA
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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:Immunobiology and natural history of human infection with agent of Lyme disease, Borrelia burgdorferi
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Project description:Sex-based differences in the immunobiology and natural history of acute and convalescent Lyme disease
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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:Ten Year Follow-up of Patients Enrolled in the Studies of Lyme disease Immunobiology and Clinical Events (SLICE)
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Project description:The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis. Experiment Overall Design: Expression profiling of ankle tissues of C3H, C57BL/6, and C57BL/6-IL10-/- mice infected with B. burgdorfer (0, 1, 2, and 4 weeks post-infection)
2008-06-14 | E-GEOD-6055 | biostudies-arrayexpress
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
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:Post-treatment Lyme Disease Symptoms/Syndrome (PTLDS) occurs in approximately 10% of Lyme disease patients following antibiotic treatment. Objective biomarkers or specific clinical symptoms to identify PTLDS patients do not currently exist and the PTLDS classification is based on the report of persistent subjective symptoms for ≥ 6 months following antibiotic treatment for Lyme disease. Untargeted liquid chromatography-mass spectrometry metabolomics was used to define metabolic changes that occurred longitudinally in PTLDS and clinically cured non-PTLDS Lyme patients from two separate cohorts. An elastic net regularization model was applied to define the metabolites that classified PTLDS and non-PTLDS patients at different time points, and the PTLDS defining metabolites were evaluated in two sample cohorts using linear discriminant analysis. This study determined that observable metabolic alterations occur between PTLDS and non-PTLDS patients at multiple time points. These metabolic alterations discriminated between PTLDS and non-PTLDS patients and consisted of metabolites of glycerophospholipid, bile acid and acylcarnitine metabolism. Longitudinal analyses showed distinct patterns in metabolite abundance changes that indicated a greater variability in PTLDS vs non-PTLDS patients. These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.
2020-05-28 | ST001391 | MetabolomicsWorkbench
Project description:Lyme disease is caused by infection with Borrelia burgdorferi, with a spectrum of clinical disorders. Murine studies with B6 and C3H mice have demonstrated that genetic differences in the host response play an essential role in regulating the severity of Lyme arthritis. C3H mice generate a robust induction of type I IFN response in joint tissue at one week of infection which leads to severe Lyme arthritis at 4 weeks post-infection, while B6 mice develop mild disease without a type I IFN profile. We used a forward genetic approach and identified B. burgdorferi arthritis- associated locus 1 (Bbaa1) on Chr4, which includes type I IFN cluster. B6.C3-Bbaa1 congenic mice display more severe Lyme arthritis than B6 mice. The blocking of type I IFN receptor and the IFNb subtype in Bbaa1 mice suppressed arthritis back to B6 level, so we concluded the Bbaa1 locus intrinsically controls IFNb production, and the differential expression of IFNb controls the severity of Lyme arthritis. However, the IFNb genes of C3H and B6 mice are identical, prompting focus on other genetic factors within the Bbaa1 locus as regulators of IFNb. Reciprocal radiation chimeras between B6.C3-Bbaa1 and B6 mice revealed myeloid cells in the joint tissue as IFNb initiators. Advanced congenic lines were generated to reduce the genetic contribution from C3H Bbaa1 region. RNA-seq of bone marrow-derived macrophages (BMDMs) from B6 and advanced interval specific recombinant congenic lines, ISRCL3 and ISRCL4, revealed novel candidates that may regulate Ifnb. In this study, we identify the Cdkn2a gene encoded ARF as a critical regulator of IFNb mediated Lyme arthritis, and investigate mechanistic interactions that modulate IFNb expression in Lyme arthritis development.
2022-02-17 | GSE181071 | GEO