The Potential of Eight Plasma Proteins as Biomarkers in Redefining Leptospirosis Diagnosis

• Published in: Journal of proteome research Vol. 23; no. 9; pp. 4027 - 4042
• Main Authors: Fish-Low, Cheng-Yee, Than, Leslie Thian Lung, Ling, King-Hwa, Sekawi, Zamberi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.09.2024
• Subjects: Acute-Phase Proteins - analysis; Adult; amyloid; apolipoprotein A-II; biomarkers; Biomarkers - blood; Blood Proteins - analysis; blood serum; C-reactive protein; C-Reactive Protein - analysis; Carrier Proteins - blood; Case-Control Studies; chemokine CXCL4; dengue; Dengue - blood; Dengue - diagnosis; diagnostic techniques; endemic diseases; family; Female; gene expression regulation; Glycoproteins; Humans; leptospirosis; Leptospirosis - blood; Leptospirosis - diagnosis; Malaysia; Male; Membrane Glycoproteins - blood; Membrane Proteins - blood; Middle Aged; mortality; Platelet Factor 4 - blood; profilins; proteome; Proteome - analysis; Proteomics - methods; seroconversion; Serum Amyloid A Protein - analysis; spectroscopy; Thrombospondin 1 - blood; Malaysia; iTRAQ; leptospirosis; biomarker; plasma proteome
• ISSN: 1535-3893; 1535-3907; 1535-3907
• DOI: 10.1021/acs.jproteome.4c00376

Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, 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 a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the “one disease, one biomarker” concept.