Oct-6 transcriptional factor a possible biomarker for leprosy diagnosis

Serrano-Coll, Héctor; Salazar-Peláez, Lina María; Mesa, Felipe; Cardona-Castro, Nora

doi:10.1016/j.diagmicrobio.2020.115232

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…Similarly, other transcriptomic studies described leprosy biomarkers associated with leprosy but after occurrence of symptoms and using skin biopsies [ 53 , 63 , 88 , 89 ]. Serrano-Coll and colleagues showed that RT-qPCR of Oct-6 identified multibacillary (MB) patients (n=30) in Colombia with an AUC of 83.0% (89].…”

Section: Discussionmentioning

confidence: 91%

Blood RNA signature RISK4LEP predicts leprosy years before clinical onset

et al. 2021

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Background Leprosy, 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. Methods We 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). Findings Although 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%). Interpretation This 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. Funding This 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).

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Section: Discussionmentioning

confidence: 91%

Blood RNA signature RISK4LEP predicts leprosy years before clinical onset

et al. 2021

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“…5,15 Conversely, identifying cutaneous nerves requires more expertise from the evaluator, even using S-100 IHC. Specifically, 1 of our criticisms of S-100, as exposed in our previous study, 8 is that the nonvisualization of the nerve fiber in the dermal nerve is usually interpreted as a pathognomonic diagnostic sign of this disease. 14,16 In addition, it is likely that the nerve fiber is not included in the sample section or that the biopsy does not include all layers of the skin.…”

Section: Discussionmentioning

confidence: 91%

“…Conversely, the staining of skin nerve fibers marked with anti-S-100 was classified using the pathological patterns described in Table 1S http://links.lww.com/AJDP/A128 (Supplementary material). 5,8…”

Section: Methodsmentioning

confidence: 99%