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.
Highlights
Leprosy is a chronic infectious disease caused mainly by the slow-growing intracellular pathogen Mycobacterium leprae that does not grow in axenic media
As for differentiating leprosy per se vs. Other dermatological diseases (ODD), genes IDO1, BLK, CD38, CXCL11, and SLAMF7, all had an area under the curve (AUC) of at least 96% with their lower bound 97% confidence intervals above 90% (Figs 2A, 3C and S6 Table)
The penalized logistic regression model, evaluated on two independent datasets, demonstrated that HS3ST2 and CD40LG hold potential to differentiate between MB and PB lesions
Summary
Leprosy is a chronic infectious disease caused mainly by the slow-growing intracellular pathogen Mycobacterium leprae that does not grow in axenic media. This bacterium resides preferentially in skin macrophages and Schwann cells in peripheral nerves, inducing dermatosis and/or neuritis. Patients can present several distinct clinical forms according to their immune response, histopathological characterization, and bacterial load. A localized tuberculoid form (TT) is characterized by low bacterial counts and a strong cellular immune response. In the opposite lepromatous (LL) pole, a disseminated form, patients exhibit several lesions, a predominantly humoral response, and a high bacterial load in the tissues [1,2,3]. For operational and treatment purposes, leprosy is classified by the World Health Organization as paucibacillary (PB) or multibacillary (MB), based on the number of skin lesions, association with nerve involvement or the bacilli detection in slit-skin smears [4]
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