Profiling renal variations and plasma proteome in human Leptospirosis

Leptospirosis, a notifiable endemic disease in Malaysia, is associated with a higher mortality rate than another prevalent disease in the region, dengue fever. However, underreporting due to asymptomatic cases, misdiagnosis, and co-infections obscures the actual disease burden. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study examined renal profile variations between leptospirosis and non-leptospirosis patients, revealing that leptospirosis patients exhibited hypocalcaemia and hypochloraemia. Additionally, the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion was compared to dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The initial iTRAQ analysis identified a total of 450 proteins and then refined them to a list of 290 proteins after a series of exclusion criteria were applied. Among these 290 proteins, a subset was differentially expressed in the leptospiraemia (85 proteins) and seroconversion (113 proteins) groups. The protein-protein interaction network identified three main protein clusters, which are associated with reverse cholesterol transport, platelet aggregation, cell-matrix adhesion, fibroblast migration, and acute-phase response. The plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins that showed significant expression variations, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following verification in a verification cohort, a panel of eight plasma protein biomarkers has been identified for leptospirosis, which are CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. These protein biomarkers align with the leptospirosis biological processes, enhancing their potential as leptospirosis diagnostic tools. In conclusion, combining renal profile differences and a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.

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