Genomewide expression profiling of multibacillary leprosy lesions before and after multi-drug therapy (MDT)

[Aim] To characterize the transcriptomic changes in skin lesions of lepromatous leprosy patients before and after multidrug therapy (MDT). Likewise, not all patients improve their bacillary index after MDT. Thus, the further analysis aims to compare patients who responded or did not to MDT and identify underlying modulated genes. [Design] Lepromatous patients were treated for 12 months with multidrug therapy. Skin biopsy samples were collected before (BT) and after treatment (AT). At the end of 12 months of MDT, those who decreased their bacillary index by at least one log10 unit were considered responders (R) and otherwise non-responders (NR). RNA was isolated, poly-A captured, and sequenced. Comparisons both within-patient and between-patients were done. [Results] At the end of MDT, genes involved with lipid metabolism, innate and adaptive immunity, extracellular matrix, and epidermis development were all differentially expressed. Comparisons between responders and non-responders to MDT identified differentially expressed genes involved with lipid metabolism, semaphorin-plexin signaling pathway, epidermis development, and vasculogenesis. This study identified gene expression signatures modulated after 12 months of MDT. Also, a subset of patients with poor bacterial clearance has dysregulated pathways relative to responders.