A new paradigm for leprosy diagnosis based on host gene expression

PLoS Pathog. 2021 Oct 25;17(10):e1009972. doi: 10.1371/journal.ppat.1009972. eCollection 2021 Oct.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Profiling
  • Genetic Markers / genetics*
  • Humans
  • Leprosy / diagnosis*
  • Leprosy / genetics*
  • RNA, Messenger / analysis
  • RNA-Seq
  • Transcriptome*


  • Genetic Markers
  • RNA, Messenger

Grant support

The first author (TLC) was supported by a PhD scholarship from Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, https://www.gov.br/cnpq/pt-br. This work was also supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, FAPERJ, grant no. 04/2015, http://www.faperj.br/; Cooperação Bilateral CB-FAPERJ/SNSF (MOM); the Fondation Raoul Follereau (STC), https://www.raoul-follereau.org/; Swiss National Science Foundation grants IZRJZ3_164174 (STC), https://www.snf.ch/en; and the Heiser Program of the New York Community Trust for Research in Leprosy, grant no. P18-000250 (MOM and CA), https://www.nycommunitytrust.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.