Genomewide expression profiling of multibacillary leprosy lesions before and after multi-drug therapy (MDT)
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PROVIDER: PRJEB52164 | ENA |
REPOSITORIES: ENA
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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:Exploratory RNA expression analysis during development of leprosy allows identification of RISK4LEP, a 4-gene blood RNA signature predicting leprosy years before clinical onset.
2021-04-23 | GSE163498 | GEO
Project description:Here we report the data generated by short-read sequencing of mRNA (polyA) isolated from granuloma annulare and leprosy skin lesions. Our main aim was to identify putative mRNA biomarkers for distinguishing leprosy from other differential diagnoses. Additionally, we also explored the distinction between MB and PB by using differential expression analysis as well as training a penalized logistic regression to select important features. Our results showed that few genes are enough to differentiate leprosy lesions, including paucibacillary cases, from other morphological and histopathological similar skin diseases. Some of these genes have been replicated in a larger and more heterogeneous sample with RT-qPCR, validating their classification potential. We also suggest important novel gene candidates to improve our understanding of molecular differences between MB and PB lesions, which could either pinpoint new pathways and targets for host-based specialized adjuvant treatment for leprosy. Finally, this dataset has been used to explore the relationship between cornification and keratinocyte-related genes and TGFB-mediated epithelial-mesenchymal transition (EMT), which could indicate that in skin, M. leprae could be de-differentiating, directly or indirectly, other cell types into a progenitor/stem-like phenotype, facilitating mycobacterial survival and migration within the host. Alternatively, this could highlight which pathways are activated during granuloma formation and/or skin barrier assembly/disassembly.
2021-10-01 | E-MTAB-10318 | biostudies-arrayexpress
Project description:In this study, a comprehensive assessment of human miRNA was performed on leprosy skin lesions using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-eight samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified differentially expressed miRNAs [Fold Change (FC)≥2.0, p<0.05] in disease lesions versus healthy controls or between them. Some of these miRNAs were validated by RT-PCR.
2017-10-31 | GSE102314 | GEO
Project description:Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN- and IL-1. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.
2021-05-04 | GSE167889 | GEO
Project description:Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections. Experiment Overall Design: 7 LL lesions, 10 BT lesions, 7 RR lesions
2009-10-30 | E-GEOD-17763 | biostudies-arrayexpress
Project description:Skin biopsy specimens of skin lesions were profiled for miRNA expression. In this study, we indentified miRNA species that were differentially expressed in the skin lesions of either the lepromatous or tuberculoid forms of leprosy. One miRNA species, hsa-mir-21, found in the lepromatous lesions was capable of downregulating the vitamin D-dependent antimicrobial pathway. Scalpel or punch skin biopsy specimens were obtained after informed consent from patients with tuberculoid leprosy and patients with lepromatous leprosy at the time of diagnosis. Specimens were embedded in OCT medium, snap-frozen in liquid nitrogen and stored at 80°C until sectioning.
2011-12-31 | E-GEOD-33192 | biostudies-arrayexpress
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:Genomewide expression profiling from peripheral blood of multibacillary leprosy and Erythema Nodosum Leprosum (ENL) before and after thalidomide treatment.
| PRJNA816146 | ENA