Parasite-derived circulating microRNAs as biomarkers for the detection of human Schistosoma japonicum infection

• Published in: Parasitology Vol. 147; no. 8; pp. 889 - 896
• Main Authors: Mu, Yi, Cai, Pengfei, Olveda, Remigio M., Ross, Allen G., Olveda, David U., McManus, Donald P.
• Format: Journal Article
• Language: English
• Published: England Cambridge University Press 01.07.2020
• Subjects: Animals; Biomarkers; Biomarkers - blood; blood serum; Circulating MicroRNA - blood; Cohort Studies; Diagnostic systems; Disease; early diagnosis; eggs; Female; Human subjects; Humans; Infections; Male; Methods; Mice; Mice, Inbred BALB C; microRNA; MicroRNAs; miRNA; Molecular Diagnostic Techniques - methods; Mollusks; Parasite Egg Count; Parasites; parasitology; Philippines; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; reverse transcriptase polymerase chain reaction; RNA, Helminth - blood; Schistosoma japonicum; Schistosoma japonicum - genetics; Schistosoma japonicum - metabolism; Schistosomiasis; Schistosomiasis japonica - diagnosis; Sensitivity and Specificity; Philippines; Australia; China; diagnosis; Biomarker; Schistosoma japonicum; schistosomiasis; Philippines; circulating miRNAs
• ISSN: 0031-1820; 1469-8161; 1469-8161
• DOI: 10.1017/S0031182019001690

Novel tools for early diagnosis and monitoring of schistosomiasis are urgently needed. This study aimed to validate parasite-derived miRNAs as potential novel biomarkers for the detection of human Schistosoma japonicum infection. A total of 21 miRNAs were initially validated by real-time-polymerase chain reaction (RT-PCR) using serum samples of S. japonicum -infected BALB/c mice. Of these, 6 miRNAs were further validated with a human cohort of individuals from a schistosomiasis-endemic area of the Philippines. RT-PCR analysis showed that two parasite-derived miRNAs (sja-miR-2b-5p and sja-miR-2c-5p) could detect infected individuals with low infection intensity with moderate sensitivity/specificity values of 66%/68% and 55%/80%, respectively. Analysis of the combined data for the two parasite miRNAs revealed a specificity of 77.4% and a sensitivity of 60.0% with an area under the curve (AUC) value of 0.6906 ( P = 0.0069); however, a duplex RT-PCR targeting both sja-miR-2b-5p and sja-miR-2c-5p did not result in an increased diagnostic performance compared with the singleplex assays. Furthermore, the serum level of sja-miR-2c-5p correlated significantly with faecal egg counts, whereas the other five miRNAs did not. Targeting S. japonicum -derived miRNAs in serum resulted in a moderate diagnostic performance when applied to a low schistosome infection intensity setting.