Genomewide expression profiling from peripheral blood of multibacillary leprosy and Erythema Nodosum Leprosum (ENL) before and after thalidomide treatment.
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ABSTRACT:
PROVIDER: PRJNA816146 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18326700_1.fastq.gz | Fastqsanger.gz | |||
| SRR18326700_2.fastq.gz | Fastqsanger.gz | |||
| SRR18326664_1.fastq.gz | Fastqsanger.gz | |||
| SRR18326664_2.fastq.gz | Fastqsanger.gz | |||
| SRR18326665_1.fastq.gz | Fastqsanger.gz |
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Project description:Acute inflammatory episodes are common in leprosy and complicate the course of the disease. Among these episodes, Erythema Nodosum Leprosum (ENL) is more common in multibacillary patients and can cause more systemic symptoms like fever, myalgia, edema, and pain. Today, ENL is managed with thalidomide and corticosteroids, yet the exact mechanisms behind ENL remain elusive and with few pharmacological options available. In this experiment, RNA was sequenced and gene expression was measured from the blood of multibacillary patients with and without ENL in a mixed design, comparing ENL to MB and ENL before and after thalidomide treatment for 7 days.
2022-03-14 | GSE198609 | GEO
Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was “cell movement” including E-selectin, which was coordinately regulated with IL-1. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1, which together with IFN-, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease. 6 ENL skin lesions and 7 Lepromatous leprosy skin lesions
2009-06-30 | E-GEOD-16844 | biostudies-arrayexpress
Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was 'cell movement' including E-selectin, which was coordinately regulated with IL-1beta. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1beta, which together with IFN-gamma, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.
2009-06-30 | GSE16844 | GEO
Project description:Genomewide expression profiling of multibacillary leprosy lesions before and after multi-drug therapy (MDT)
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Project description:Background: Reactions in Leprosy are immune exacerbations that cause debilitating consequences like nerve damage and permanent deformities. Prediction of these reactional states using appropriate biomarkers would enable early treatment interventions to prevent nerve function impairment. The current study investigated whole transcriptomic expression profiles of Mycobacterium leprae (M. leprae) that differentiate leprosy cases in type 2 (Erythema Nodosum Leprosum) reactions with those without reactions in host skin tissue derived RNA. Methods: Post clinical examination, excisional skin biopsy specimens were collected from skin lesions of subjects with and without type 2 reaction. Total RNA was extracted following the Trizol protocol and bacterial RNA was enriched in the samples. A 2 x 400K gene expression array (whole genome tiling array) was designed with the probes having 60-mer oligonucleotides tiling every 10bp of the genome sequence of M. leprae (NC_011896.1). The array comprised 420288 features which include probes and Agilent controls. The quality of RNA was estimated using BioAnalyzer (Agilent Technologies) followed by labelling, reverse transcription, amplification and hybridization to the arrays. The hybridized slides were scanned on a G2600D scanner (Agilent Technologies). The data thus acquired is analysed using GeneSpring GX Version 12.1 software. Data was normalized and fold difference in expression was noted from 359,922 probes which include sense and antisense orientations of 179,961 probes. The differentially expressing M. leprae genomic regions between type 2 reactions and non reactional cases were noted. Results: Considering a statistical cut-off value of 0.6 for fold difference in expression between the test and the control samples, a set of 107 genes indicated statistically significant up-regulation with volcano plot p-values less than 0.05. Functional characterization revealed higher-expression of genes encoding transmembrane proteins (12), regulatory proteins (9), fatty acid biosynthesis (6), amino acid metabolism (13), nucleic acid metabolism (7), DNA replication and repair (7), Secretory proteins (2) Krebs Cycle (1), Glycolysis (1), Drug Efflux Protein (1),Stress Response Protein (1), Energy Metabolism (2), Pantothenate biosynthesis (1), Metalloproteins (3), Hydrolases (1) and Hypothetical Proteins (40). Additionally there are 157 genes that are down regulated in cases with reaction. Conclusion: Differential expression of genes in the human skin biopsy specimens among leprosy cases with type 2 reaction in contrast to those without reaction suggests the role of pathogen associated gene expression triggers with the aetiology of these reactions. As most of the transmembrane and cell wall proteins possess epitope and surface exposed domains, higher expression levels of genes encoding these proteins may have a possible role in enhancing host immune responses characteristic of type 2 reactions in leprosy.
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Project description:Exploratory RNA expression analysis during development of leprosy allows identification of RISK4LEP, a 4-gene blood RNA signature predicting leprosy years before clinical onset.
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Project description:Transcriptome profiles derived from the site of human disease has led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene co-expression modules by cell type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach towards identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.
2016-08-30 | GSE84893 | GEO
Project description:[Aim] To characterize the transcriptomic changes in skin lesions of lepromatous leprosy patients before and after multidrug therapy (MDT). Likewise, not all patients improve their bacillary index after MDT. Thus, the further analysis aims to compare patients who responded or did not to MDT and identify underlying modulated genes. [Design] Lepromatous patients were treated for 12 months with multidrug therapy. Skin biopsy samples were collected before (BT) and after treatment (AT). At the end of 12 months of MDT, those who decreased their bacillary index by at least one log10 unit were considered responders (R) and otherwise non-responders (NR). RNA was isolated, poly-A captured, and sequenced. Comparisons both within-patient and between-patients were done. [Results] At the end of MDT, genes involved with lipid metabolism, innate and adaptive immunity, extracellular matrix, and epidermis development were all differentially expressed. Comparisons between responders and non-responders to MDT identified differentially expressed genes involved with lipid metabolism, semaphorin-plexin signaling pathway, epidermis development, and vasculogenesis. This study identified gene expression signatures modulated after 12 months of MDT. Also, a subset of patients with poor bacterial clearance has dysregulated pathways relative to responders.
2022-04-10 | E-MTAB-11605 | biostudies-arrayexpress
Project description:Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients. Early intervention to prevent T1R and, hence, nerve damage, is a major focus of current leprosy control efforts. In this study, we compared transcript (i.e. isoform) expression and usage profiles from leprosy patients free of T1R at enrollment (who eventually developed T1R) against T1R-free leprosy patients. Our results showed that, at baseline, cells from T1R-destined and T1R-free subjects had no main difference in their transcripts expression and usage. However, the cells of T1R patients displayed a transcriptomic immune response to M. leprae antigens that was significantly different from the one of cells from leprosy patients who remained T1R-free. Transcripts with significantly higher upregulation in the T1R-destined group, compared to the cells from T1R-free patients, were enriched for pathways and GO terms involved in response to intracellular pathogens, apoptosis regulation and inflammatory processes. Similarly, transcript usage analysis pinpointed different transcript proportions in response to the in-vitro challenge of cells from T1R-destined patients. Hence, transcript usage in concert with transcript expression suggested a dysregulated inflammatory response including increased apoptosis regulation in the peripheral blood cells of T1R-destined patients before the onset of T1R symptoms. Combined, these results provided detailed insight into the pathogenesis of T1R.
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