title: Gene set signature of reversal reaction type I in leprosy patients.
abstract: 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.
authors.affiliation: McGill International TB Centre, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Orlova
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cobat
authors.forename: Nguyen Thu
authors.initials: NT
authors.lastname: Huong
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Ba
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Thuc
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.forename: Yohann
authors.initials: Y
authors.lastname: Nédélec
authors.forename: Luis
authors.initials: L
authors.lastname: Barreiro
authors.forename: Vu Hong
authors.initials: VH
authors.lastname: Thai
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcaïs
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood* / Q000302:isolation & purification; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood; D007918:Leprosy / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D009166:Mycobacterium leprae / Q000235:genetics* / Q000472:pathogenicity; D009410:Nerve Degeneration / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D012189:Retrospective Studies
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma