Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
Medical Genetics Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
J Proteome Res. 2024 Sep 6;23(9):4027-4042. doi: 10.1021/acs.jproteome.4c00376. Epub 2024 Aug 16.
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.
钩端螺旋体病是马来西亚的一种法定地方性传染病，其死亡率高于本地区的登革热。该病具有多样化的临床症状和有限的诊断方法，这使得钩端螺旋体病的诊断变得复杂。对基于准确生物标志物的诊断方法的需求正在增加。本研究采用同位素相对标记与绝对定量（iTRAQ）-质谱（MS）法，对伴有菌血症和血清学转换的钩端螺旋体病患者、登革热患者和健康对照者的血浆蛋白质组进行了研究。iTRAQ 分析共鉴定出 450 种蛋白质，通过一系列排除标准，进一步精减为 290 种蛋白质。与对照组相比，在钩端螺旋体病患者的血浆蛋白质组中差异表达的蛋白有 11 种，包括载脂蛋白 A-II（APOA2）、C 反应蛋白（CRP）、FERMT3 同源物 3（FERMT3）、富含亮氨酸α-2-糖蛋白 1（LRG1）、脂多糖结合蛋白（LBP）、肌球蛋白-9（MYH9）、血小板碱性蛋白（PPBP）、血小板因子 4（PF4）、原肌球蛋白-1（PFN1）、血清淀粉样蛋白 A-1 蛋白（SAA1）和血栓反应蛋白-1（THBS1）。在对验证队列进行研究后，确定了 8 种有潜在应用价值的血浆蛋白生物标志物用于钩端螺旋体病的诊断：CRP、LRG1、LBP、MYH9、PPBP、PF4、SAA1 和 THBS1。总之，这 8 种蛋白质生物标志物的组合为钩端螺旋体病的诊断提供了一种很有前途的方法，解决了“一种疾病，一种生物标志物”概念的局限性。
