01897nas a2200241   4500000000100000008004100001260001200042100001700054700001300071700001300084700001300097700001200110700001500122700001200137700001100149700001300160245007200173856010400245300001300349490000700362520127200369022001401641       2021                            d  c10/20211 aLeal-Calvo T1 aAvanzi C1 aMendes M1 aBenjak A1 aBusso P1 aPinheiro R1 aSarno E1 aCole S1 aMoraes M00aA new paradigm for leprosy diagnosis based on host gene expression.  uhttps://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009972&type=printable  ae10099720 v173 a<p>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.</p>  a1553-7374