Fibrosin: A Candidate Biomarker of Schistosomal Liver Fibrosis in Humans

纤维蛋白：人类血吸虫性肝纤维化的候选生物标志物

• 批准号: 8509427
• 负责人: DAVID J WYLER
• 金额: $ 7.95万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509427
• 关键词: Affinity Chromatography; Age; Antibodies; Antigen Targeting; Area; Biological Assay; Biological Markers; Cell Line; Chronic; Cloning; Cohort Studies; Cross-Sectional Studies; Development; Diagnostic tests; Disease Management; Enzyme-Linked Immunosorbent Assay; Fibrosis; Future; Gender; Goals; Hepatic Fibrogenesis; Human; Hybridomas; Immunoassay; Immunoglobulin G; Inbred BALB C Mice; Individual; Infection; Life; Liver Fibrosis; Measures; Methods; Monitor; Morbidity - disease rate; Multiple Myeloma; Mus; Nutritional status; Oryctolagus cuniculus; Ovalbumin; Patients; Peptides; Philippines; Platyhelminths; Praziquantel; Publishing; Research; Risk; Role; Sampling; Schistosoma; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Serum; Socioeconomic Status; Source; Splenocyte; Translations; Ultrasonography; Work; base; chemotherapy; cohort; disability; epidemiologic data; fibrosin; follow-up; health economics; longitudinal analysis; programs; public health priorities; public health relevance; response; sex; treatment program

DESCRIPTION (provided by applicant): Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas [1]. Although schistosomiasis is effectively treated with praziquantel (PZQ), rapid reinfection with rebound morbidity and fibrosis precludes effective control based on chemotherapy alone. The resubmission of our R03 application seeks to develop a quantitative immunoassay for fibrosin and apply it to epidemiologically well-characterized sera already collected and available from a longitudinal cohort study of Schistosoma japonicum-infected patients (n=616). The principle goal is to determine whether serum fibrosin concentrations are associated with concurrent hepatic fibrosis and whether baseline serum fibrosin levels predict hepatic fibrosis one year post-PZQ treatment. The work serves as the first translation to human research of extensive related studies of S. mansoni-infected mice that led to the discovery of fibrosin and its apparent role in hepatic fibrogenesis. Based on our published observations in infected mice (and in a small preliminary study of S. mansoni-infected patients,) we anticipate that patients infected with S. japonicum will have significantly elevated serum fibrosin concentrations compared to uninfected controls, and that those with ultrsonographically-demonstrable liver fibrosis will have the highest levels. Furthermore, we anticipate that fibrosin levels measured in serum collected from S. japonicum infected individuals 4 weeks post-PZQ will be significantly higher in patients who develop fibrosis at one yr of follow-up compared to levels in patients who do not develop fibrosis at a one-year follow-up assessment. Such a biomarker for patients at risk of developing fibrosis has the potential to profoundly influence disease management. Specifically, a rapid diagnostic test (RDT) for fibrosin could identify those individuals at risk of hepatic fibrosis and prioritize them from more frequent PZQ treatment.

描述（由申请人提供）：血吸虫病，是由三种主要种类的雌雄异源性杂种（Flatemats）引起的，目前感染了超过2.5亿的人，导致估计2-15％的慢性残疾，并导致了地方性地区的健康和经济停滞状况不佳[1]。尽管血吸虫病有效地用praziquantel（PZQ）治疗，但通过反弹发病率和纤维化的快速再感染，仅基于化学疗法就无法有效控制。 我们的R03应用程序的重新提取旨在开发用于纤维素的定量免疫测定法，并将其应用于已经收集的流行病学良好的血清，并从japonicum感染的患者的纵向同类研究中获得（n = 616）。主要目标是确定血清纤维素浓度是否与并发肝纤维化以及基线血清纤维素水平是否相关，是否可以预测PZQ后一年的肝纤维化。这项工作是对曼氏链球菌感染小鼠的广泛相关研究的人类研究的首次转化，该研究导致发现纤维素及其在肝纤维发生中的明显作用。基于我们在感染小鼠中发表的观察结果（在对曼氏链球菌感染的患者的少量初步研究中），我们预计与未感染的对照相比，患有japonicum链球菌的患者的血清纤维蛋白浓度将显着升高，而患有大量肝纤维化的患者将具有最高水平。此外，我们预计，与未在一年的随访评估时未发展纤维化的患者相比，在一年的随访中，在一年的随访中，在一年的随访水平中，PZQ 4周的血清中测得的纤维素水平将显着更高。这种生物标志物适用于患有纤维化风险的患者，有可能对疾病管理产生深远的影响。具体而言，纤维素的快速诊断测试（RDT）可以识别那些有肝纤维化风险的人，并通过更频繁的PZQ治疗将其优先考虑。