Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
PLoS Negl Trop Dis. 2013 May 23;7(5):e2228. doi: 10.1371/journal.pntd.0002228. Print 2013.
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.
大约有 6.8 亿人面临感染华支睾吸虫（OV）和中华分支睾吸虫的风险，仅在东南亚地区就估计有 1000 万人感染 OV。虽然华支睾吸虫病与肝胆病理有关，如胆管周围纤维化（APF）和胆管癌（CCA），但 OV 感染的动物模型表明，免疫复合物肾小球肾炎是一种重要的肾脏病理，与肝胆病理同时发生。免疫复合物肾小球肾炎的一个主要特征是免疫球蛋白 G（IgG）的尿液排泄（微量蛋白尿）。在泰国东北部奇河沿岸 OV 流行地区的社区研究中，我们观察到超过一半的参与者尿液中针对粗 OV 抗原提取物（OV 抗原）的 IgG 呈阳性。我们还观察到，尿液 IgG 对 OV 抗原的升高水平与 OV 感染的强度无关，但可能是由 OV 感染的动物模型中所见的免疫复合物肾小球肾炎引起的。此外，我们观察到在 APF 患者和 CCA 患者中，尿液 IgG 对 OV 抗原的排泄浓度分别比对照组高 21 倍和 158 倍。我们还观察到，尿液 IgG 对 OV 抗原的升高可以将 APF+和 CCA+个体与非病例个体区分开来。最后，尿液 IgG 对 OV 抗原呈阳性的个体发生 APF 的风险更高，OR 值为 6.69（95%CI：2.87，15.58），发生 CCA 的风险更高，OR 值为 71.13（95%CI：15.13，334.0）比尿液中没有检测到 OV 抗原 IgG 的个体更高。在此，我们首次展示了 OV 流行地区广泛的肾脏病理负担，并且尿液生物标志物可用于估计 OV 感染期间肾脏和肝胆病理的风险，即作为华支睾吸虫病晚期病理的“综合征生物标志物”。
