A new paradigm for leprosy diagnosis based on host gene expression

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for p...

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Bibliographic Details
Published in:	PLoS pathogens 2021-10, Vol.17 (10), p.e1009972-e1009972
Main Authors:	Leal-Calvo, Thyago, Avanzi, Charlotte, Mendes, Mayara Abud, Benjak, Andrej, Busso, Philippe, Pinheiro, Roberta Olmo, Sarno, Euzenir Nunes, Cole, Stewart Thomas, Moraes, Milton Ozório
Format:	Article
Language:	eng
Subjects:	Analysis Biology and Life Sciences CD38 antigen Cluster analysis Confidence intervals Diagnosis Erythema Gene amplification Gene expression Gene sequencing Genes Genetic aspects Granuloma Granulomas Immune response Immune response (cell-mediated) Leprosy Lipids Medicine and Health Sciences Mesenchyme Molecular diagnostic techniques Phagocytes Principal components analysis Psoriasis Research and analysis methods Ribonucleic acid RNA RNA sequencing Skin Skin diseases Skin lesions Therapeutic applications Transcription Transcriptomes Tryptophan 2,3-dioxygenase
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Summary:	Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.
ISSN:	1553-7374 1553-7366 1553-7374