Miele Gino, Seeger Harald, Marino Denis, Eberhard Ralf, Heikenwalder Mathias, Stoeck Katharina, Basagni Max, Knight Richard, Green Alison, Chianini Francesca, Wüthrich Rudolf P, Hock Christoph, Zerr Inga, Aguzzi Adriano
Department of Pathology, UniversitätsSpital Zürich, Institute of Neuropathology, Zürich, Switzerland.
PLoS One. 2008;3(12):e3870. doi: 10.1371/journal.pone.0003870. Epub 2008 Dec 5.
The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that alpha(1)-antichymotrypsin (alpha(1)-ACT) was highly upregulated in brains of scrapie-infected mice. Furthermore, alpha(1)-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased alpha(1)-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary alpha(1)-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections.
血源性朊病毒传播事件的发生需要识别潜在的朊病毒携带者。然而，目前用于朊病毒病活体诊断的方法依赖于侵入性组织活检，不适用于大规模筛查。敏感的生物标志物可能有助于满足这一需求。在这里，我们扫描了基因组，寻找朊病毒感染后升高且编码分泌蛋白的转录本。我们发现，α(1)-抗糜蛋白酶（α(1)-ACT）在感染羊瘙痒病的小鼠大脑中高度上调。此外，散发性克雅氏病患者尿液中的α(1)-ACT水平显著升高，且在整个疾病过程中逐渐增加。在动物自然感染朊病毒病的病例中也发现α(1)-ACT排泄增加。因此，测量尿中α(1)-ACT水平可能有助于监测朊病毒病治疗方案的疗效，也可能有助于推迟可能有传播朊病毒感染风险的血液和器官捐献者。
