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Gene Set Signature of Reversal Reaction Type I in Leprosy Patients
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نویسنده
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orlova m. ,cobat a. ,huong n.t. ,ba n.n. ,van thuc n. ,spencer j. ,nédélec y. ,barreiro l. ,thai v.h. ,abel l. ,alcaïs a. ,schurr e.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 7
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چکیده
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Leprosy reversal reactions type 1 (t1r) are acute immune episodes that affect a subset of leprosy patients and remain a major cause of nerve damage. little is known about the relative importance of innate versus environmental factors in the pathogenesis of t1r. in a retrospective design,we evaluated innate differences in response to mycobacterium leprae between healthy individuals and former leprosy patients affected or free of t1r by analyzing the transcriptome response of whole blood to m. leprae sonicate. validation of results was conducted in a subsequent prospective study. we observed the differential expression of 581 genes upon exposure of whole blood to m. leprae sonicate in the retrospective study. we defined a 44 t1r gene set signature of differentially regulated genes. the majority of the t1r set genes were represented by three functional groups: i) pro-inflammatory regulators; ii) arachidonic acid metabolism mediators; and iii) regulators of anti-inflammation. the validity of the t1r gene set signature was replicated in the prospective arm of the study. the t1r genetic signature encompasses genes encoding pro- and anti-inflammatory mediators of innate immunity. this suggests an innate defect in the regulation of the inflammatory response to m. leprae antigens. the identified t1r gene set represents a critical first step towards a genetic profile of leprosy patients who are at increased risk of t1r and concomitant nerve damage. © 2013 orlova et al.
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آدرس
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mcgill international tb centre,the research institute of the mcgill university health centre,montreal,qc, Canada, mcgill international tb centre,the research institute of the mcgill university health centre,montreal,qc,canada,departments of human genetics and medicine,mcgill university,montreal,qc, Canada, hospital for dermato-venereology,ho chi minh city, Viet Nam, hospital for dermato-venereology,ho chi minh city, Viet Nam, hospital for dermato-venereology,ho chi minh city, Viet Nam, department of microbiology,immunology and pathology,college of veterinary medicine and biomedical sciences,colorado state university,fort collins,co, United States, department of pediatrics,sainte-justine hospital research centre,university of montreal,montreal,qc, Canada, department of pediatrics,sainte-justine hospital research centre,university of montreal,montreal,qc, Canada, hospital for dermato-venereology,ho chi minh city, Viet Nam, laboratory of human genetics of infectious diseases,necker branch,institut national de la santé et de la recherche médicale,paris,france,university paris descartes,imagine institute,paris,france,st. giles laboratory of human genetics of infectious diseases,rockefeller branch,the rockefeller university,ny,ny, United States, laboratory of human genetics of infectious diseases,necker branch,institut national de la santé et de la recherche médicale,paris,france,university paris descartes,imagine institute,paris,france,st. giles laboratory of human genetics of infectious diseases,rockefeller branch,the rockefeller university,ny,ny,united states,urc-cic,hopital tarnier,paris, France, mcgill international tb centre,the research institute of the mcgill university health centre,montreal,qc,canada,departments of human genetics and medicine,mcgill university,montreal,qc, Canada
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Authors
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