1. Microproteinuria during Opisthorchis viverrini Infection: A Biomarker for Advanced Renal and Hepatobiliary Pathologies from Chronic Opisthorchiasis.
- Author
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Saichua, Prasert, Sithithaworn, Paiboon, Jariwala, Amar R., Deimert, David J., Sithithaworn, Jiraporn, Sripa, Banchob, Laha, Thewarach, Mairiang, Eimorn, Pairojkul, Chawalit, Periago, Maria Victoria, Khuntikeo, Narong, Mulvenna, Jason, and Bethony, Jeffrey M.
- Subjects
OPISTHORCHIS viverrini ,CHOLANGIOCARCINOMA ,CLONORCHIS sinensis ,BIOMARKERS ,NEPHRITIS ,BILE ducts - Abstract
Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) and Clonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of the participants had urine IgG against a crude OV antigen extract (OV antigen). We also observed that elevated levels of urine IgG to OV antigen were not associated with the intensity of OV infection, but were likely the result of immune-complex glomerulonephritis as seen in animal models of OV infection. Moreover, we observed that urine IgG to OV antigen was excreted at concentrations 21 times higher in individuals with APF and 158 times higher in individuals with CCA than controls. We also observed that elevated urine IgG to OV antigen could identify APF+ and CCA+ individuals from non-cases. Finally, individuals with urine IgG to OV antigen had a greater risk of APF as determined by Odds Ratios (OR = 6.69; 95%CI: 2.87, 15.58) and a greater risk of CCA (OR = 71.13; 95%CI: 15.13, 334.0) than individuals with no detectable level of urine IgG to OV antigen. Herein, we show for the first time the extensive burden of renal pathology in OV endemic areas and that a urine biomarker could serve to estimate risk for both renal and hepatobiliary pathologies during OV infection, i.e., serve as a "syndromic biomarker" of the advanced pathologies from opisthorchiasis. Author Summary: Approximately 680 million people risk infection with food-borne trematodes, including Opisthorchis viverrini (OV). Animal models show that significant kidney pathology results from OV infection as detected by antibodies in urine (microproteinuria). However, kidney pathology in humans infected with OV is often overlooked because it develops alongside more severe pathologies such as bile duct fibrosis and bile duct cancer. In Northeastern Thailand, the researchers observed that OV infected individuals had elevated levels of urine IgG against OV antigen that was not associated with the level of OV infection. The researchers observed that urine IgG to OV antigen was associated with bile duct fibrosis and bile duct cancer. Moreover, individuals with urine IgG to OV antigen also had elevated risk of bile duct fibrosis and bile duct cancer than individuals with no urine IgG to OV antigen. For the first time, OV infection has been shown to result in significant kidney disease in humans, which is also strongly associated with bile duct pathology. A urine-based assay that could indicate both renal and bile duct pathology from OV infection would be of profound benefit in Southeast Asia, especially in the resource-limited settings of the Mekong Basin region countries of Thailand, Laos and Cambodia. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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