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A NEW PARADIGM FOR LEPROSY DIAGNOSIS BASED ON HOST GENE EXPRESSION
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland / Current address: Department for BioMedical Research, Oncogenomics Laboratory. University of Bern. Bern, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Global Health Institute, École Polytechnique Fédérale de Lausanne. Lausanne, Switzerland / Current address: Department for BioMedical Research, Oncogenomics Laboratory. University of Bern. Bern, Switzerland.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Abstract
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.
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