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Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms

ABSTRACT: Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms

PROVIDER: PRJNA1120421 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29294400_1.fastq.gz	Fastqsanger.gz
	SRR29294400_2.fastq.gz	Fastqsanger.gz
	SRR29294401_1.fastq.gz	Fastqsanger.gz
	SRR29294401_2.fastq.gz	Fastqsanger.gz
	SRR29294402_1.fastq.gz	Fastqsanger.gz

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Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms

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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Blood RNA signature RISK4LEP predicts leprosy years before clinical onset

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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Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

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.

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Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

Project description:Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

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Transcriptome analysis in Human leprosy patients

Project description:Leprosy is classified from paucibacillary leprosy (TT and BT) to multibacillary leprosy (BB, BL, and LL). In our study, we focus on selecting or classfying the significant genes to discriminate between paucibacillary and multibacillary group and the important genes to distinguish between blood and the corresponding tissue in patients. · Human Adult Normal Skin Sample (Commercial;Cat#1234218); 6 patients of leprosy (Blood and Tissue sample (Pathologic classification: BT); 6 patients of leprosy (Blood and Tissue sample (Pathologic classification: MB)) · In blood sample, BT sample vs MB sample · In tissue sample, Normal Skin sample vs tissue BT sample or tissue MB sample · Single Color Microarray · All experiments are performed one replicate

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2011-03-17 | GSE24280 | GEO

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Project description:Comparison of single cell RNA sequencing in leprosy lesions from lepromatous and reversal reaction patients

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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

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