Abstract
Opisthorchiasis caused by Opisthorchis viverrini induces periductal fibrosis via host immune/inflammatory responses. Plasma protein alteration during host-parasite interaction-mediated inflammation may provide potential diagnostic and/or prognostic biomarkers. To search for target protein changes in O. viverrini-infected hamsters, a 1-D PAGE gel band was trypsin-digested and analyzed by a LC-MS/MS-based proteomics approach in the plasma profile of infected hamsters, and applied to humans. Sixty seven proteins were selected for further analysis based on at least two unique tryptic peptides with protein ID score >10 and increased expression at least two times across time points. These proteins have not been previously identified in O. viverrini-associated infection. Among those, proteins involved in structural (19%), immune response (13%), cell cycle (10%) and transcription (10%) were highly expressed. Western blots revealed an expression level of protein tyrosine phosphatase alpha (PTPα) which reached a peak at 1 month and subsequently tended to decrease. Fibronectin significantly increased at 1 month and tended to increase with time, supporting proteomic analysis. PTPα was expressed in the cytoplasm of inflammatory cells, while fibronectin was observed mainly in the cytoplasm of fibroblasts and the extracellular matrix at periductal fibrosis areas. In addition, these protein levels significantly increased in the plasma of O. viverrini-infected patients compared to healthy individuals, and significantly decreased at 2-months post-treatment, indicating their potential as disease markers. In conclusion, our results suggest that plasma PTPα and fibronectin may be associated with opisthorchiasis and the hamster model provides the basis for development of novel diagnostic markers in the future.
Highlights
Opisthorchiasis caused by infection with the liver fluke Opisthorchis viverrini remains a major health problem in large parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia
In acute O. viverrini infections the major histopathological changes include the accumulation of inflammatory cells, nitric oxide (NO)-mediated DNA damage and liver tissue injury [5]
The relationship between periductal fibrosis and CCA suggests that expression changes in biomolecules involved in inflammation, such as those provoked by DNA damage [10], etheno DNA adducts [11] and other fibrotic markers could be used as prognostic marker of opisthorchiasis-associated CCA in humans
Summary
Opisthorchiasis caused by infection with the liver fluke Opisthorchis viverrini remains a major health problem in large parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. In acute O. viverrini infections the major histopathological changes include the accumulation of inflammatory cells, nitric oxide (NO)-mediated DNA damage and liver tissue injury [5]. This makes diagnosis of O. viverrini infection difficult as these changes are clinically silent and generally only detected after ultrasound imaging in severe cases of chronic infection [6]. The relationship between periductal fibrosis and CCA suggests that expression changes in biomolecules involved in inflammation, such as those provoked by DNA damage [10], etheno DNA adducts [11] and other fibrotic markers could be used as prognostic marker of opisthorchiasis-associated CCA in humans. Plasma contains all tissue proteins leakage [12], which may serve as protein-disease markers discovery
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