Blood RNA signature RISK4LEP predicts leprosy years before clinical onset
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163498 | GEO | 2021/04/23
REPOSITORIES: GEO
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Project description:Blood RNA signature RISK4LEP predicts leprosy years before clinical onset
| PRJNA686397 | ENA
Project description:BackgroundLeprosy, a chronic infectious disease caused by Mycobacterium leprae, is often late- or misdiagnosed leading to irreversible disabilities. Blood transcriptomic biomarkers that prospectively predict those who progress to leprosy (progressors) would allow early diagnosis, better treatment outcomes and facilitate interventions aimed at stopping bacterial transmission. To identify potential risk signatures of leprosy, we collected whole blood of household contacts (HC, n=5,352) of leprosy patients, including individuals who were diagnosed with leprosy 4-61 months after sample collection.MethodsWe investigated differential gene expression (DGE) by RNA-Seq between progressors before presence of symptoms (n=40) and HC (n=40), as well as longitudinal DGE within each progressor. A prospective leprosy signature was identified using a machine learning approach (Random Forest) and validated using reverse transcription quantitative PCR (RT-qPCR).FindingsAlthough no significant intra-individual longitudinal variation within leprosy progressors was identified, 1,613 genes were differentially expressed in progressors before diagnosis compared to HC. We identified a 13-gene prospective risk signature with an Area Under the Curve (AUC) of 95.2%. Validation of this RNA-Seq signature in an additional set of progressors (n=43) and HC (n=43) by RT-qPCR, resulted in a final 4-gene signature, designated RISK4LEP (MT-ND2, REX1BD, TPGS1, UBC) (AUC=86.4%).InterpretationThis study identifies for the first time a prospective transcriptional risk signature in blood predicting development of leprosy 4 to 61 months before clinical diagnosis. Assessment of this signature in contacts of leprosy patients can function as an adjunct diagnostic tool to target implementation of interventions to restrain leprosy development.FundingThis study was supported by R2STOP Research grant, the Order of Malta-Grants-for-Leprosy-Research, the Q.M. Gastmann-Wichers Foundation and the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP# 702.02.73 and # 703.15.07).
| S-EPMC8182229 | biostudies-literature
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.
2024-12-03 | GSE269151 | GEO
Project description:We evaluated the predictive ability of various gene signatures in baseline peripheral blood mononuclear cell samples to distinguish Mtb-infected individuals who eventually progress to TB disease (progressors) or who remain asymptomatic (non-progressors) during clinical follow-up; we also compare long-term Mtb-infected non-progressors from patients with TB disease
2020-02-25 | GSE112104 | GEO
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
2011-03-17 | E-GEOD-24280 | biostudies-arrayexpress
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.
2011-03-17 | GSE24280 | GEO
Project description:Leprosy Transcriptome (mRNA)
| PRJEB39246 | ENA
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:Inflammaging is the name given to this chronic and asymptomatic inflammatory state generated by the aging process and by chronic and infectious diseases. Chronic diseases can alter the epigenetic profile of tissues leading to an increased epigenetic aging and some of the differentially methylated genes can be used to characterize the disease and as disease biomarkers. Leprosy is an infection caused by Mycobacterium leprae and can be lifelong, exposing the individual to a low-grade inflammation environment. In this study, we evaluated the inflammatory profile in 35 individuals from a leprosy endemic area from Brazil by cytokine analysis with a luminex assay. In adition, we investigated the leucocytes genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip array. A total number of 31 CpGs were significantly methylated, between cases and controls, which belonged to 8 genes potentially peripherally perturbed in the pathogenesis of the disease. Affected individuals from endemic area were epigenetically aged in relation to control samples and interesting control samples from endemic area were aged in relation to unaffected control samples from non-endemic area. In conclusion, leprosy showed a deregulated methylation profile in comparison with control samples. The epigenetic analysis provided valuable clues for further investigations in understanding peripherical blood leprosy alterations and the use of these genes as biomarkers.
2023-02-21 | GSE197331 | 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