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We aimed to identify an unique host transcriptional signature in peripheral blood mononuclear cells (PBMCs) in response to  Mycobacterium leprae  antigens to distinguish between patients with leprosy and non-leprosy controls for early diagnosis of the disease. Sixteen individuals were enrolled in the discovery cohort [eight patients with leprosy, comprising four multibacillary (MB) and four paucibacillary (PB); and eight non-leprosy controls, comprising four healthy house contacts (HHCs) and four endemic controls (ECs)]. The differences in the transcriptome response of PBMCs to  M. leprae  sonicate antigen were evaluated between leprosy patients and non-leprosy controls, and 12 differentially expressed genes ( CCL2/MCP-1 ,  IL-8 ,  JAKM ,  ATP, ND1 ,  SERP ,  FLJ10489 ,  LINC00659 ,  LOC34487 ,  LOC101928143 ,  MIR22 , and  NCF1C ) were identified. The accuracy of the 12 differentially expressed genes was further validated for the diagnosis of leprosy using real-time quantitative PCR in 82 individuals (13 MB, 10 PB, 37 HHCs, and 22 ECs) in the validation cohort. We found that a 5 gene signature set  IL-8 ,  CCL2/MCP-1 ,  SERP ,  LINC00659  and  FLJ10489  had a suitable performance in discriminating leprosy from ECs. In addition, elevated expression of  IL-8 ,  CCL2/MCP-1 ,  SERP  and  LINC00659  was associated with MB diagnosis compared with ECs, whereas increased expression of  IL-8 ,  CCL2/MCP-1 ,  SERP  and  FLJ10489  was found to be useful biomarkers for PB diagnosis from ECs. Moreover, we found decreased expression of  NCF1C  among leprosy patients could distinguish leprosy from HHCs, whereas higher expression of  CCL2  among MB than PB could distinguish different leprosy patients. In conclusion, among the 12 candidate host genes identified, a three gene signature  IL-8, CCL2/MCP-1 , and  SERP  showed the best performance in distinguishing leprosy patients from healthy controls. These findings may have implications for developing a rapid blood-based test for early diagnosis of leprosy.

frontiers in cellular and infection microbiology

Transcriptomic Analysis of Mycobacterium leprae-Stimulated Response in Peripheral Blood Mononuclear Cells Reveal Potential Biomarkers for Early Diagnosis of Leprosy