Circulating microtranscriptome profiles reveal distinct expression of microRNAs in severe leptospirosis

Abstract

Biomarkers to predict the severity of leptospirosis are still lacking. This study aimed to identify and validate microRNAs in patients with severe leptospirosis, that could potentially be used as biomarkers for predicting an unfavorable outcome. Serum samples were collected from participants with definite diagnosis of leptospirosis. The participants were divided into two groups, non-severe and severe leptospirosis, as defined by the Specific Organ Sequential Organ Failure (SOFA) Score of more than two in any organ. Microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs was then validated by quantitative RT-PCR. Based on the NanoString, the microtranscriptome profile of the severe group was significantly different from that of the non-severe group. Upregulation of miR155-5p, miR362-3p, miR502-5p, miR601, miR1323, and miR630 in the severe group were identified, and further investigated. A total of 119 participants were enrolled in the validation cohort. Serum miR155-5p and miR630 levels were significantly higher in the severe group compared to the non-severe group. The combined use of miR155-5p or miR-630 with serum bicarbonate levels had an AUC of 0.79 (95%CI; 0.69–0.89, p<0.001) in identifying the severity of the disease. This data provides the first evidence that the microtranscriptome profiles of patients with severe leptospirosis were different from the non-severe group. Serum miR155-5p and miR630 levels might be novel biomarkers for identifying severe leptospirosis.

Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis

“…Moreover, a previous study identified specific miRNAs that were able to discriminate the infection from other acute febrile diseases with a high sensitivity and specificity [ 21 ]. Additionally, our group recently demonstrated distinct expression of circulating microRNAs as novel biomarkers for identifying severe leptospirosis [ 22 ]. However, there is very limited information regarding the expression of circulating miRNAs in patients with leptospirosis in the context of liver-related complications.…”

Acute kidney injury in the tropics

“…Endothelial injury markers already observed in leptospirosis‐associated AKI are the intercellular adhesion molecule‐1 (ICAM‐1) and syndecan‐1 22 . The difference in microtranscriptome profiles, including serum miR155‐5p and miR630, was shown as a possible biomarker for patients with severe versus non‐severe leptospirosis 36 . Diagnostic tests recommended by World Health Organization (WHO) including microscopic agglutination test (MAT), direct culture and polymerase chain reaction technique require advanced facilities which are not universally available 37 .…”

“…22 The difference in microtranscriptome profiles, including serum miR155-5p and miR630, was shown as a possible biomarker for patients with severe versus non-severe leptospirosis. 36 Diagnostic tests recommended by World Health Organization (WHO) F I G U R E 1 Pathogenesis of leptospirosis-associated AKI and factors associated with severity of leptospirosis-associated AKI. Leptospira migrate to the renal tubulointerstitium.…”