mBio两项新技术更快诊断特殊传染病

　　

生物通报道：莱姆症（Lyme Disease）是一种人畜共通传染病，最早于1975年发生在美国康乃狄克州的莱姆镇而由此得名。这种疾病是最常见的由虱子传播的传染病，其真正病原是螺旋体细菌类的伯氏疏螺旋菌（Borrelia burgdorferi），这种细菌还能导致人类发生关节炎，去年加拿大女歌手艾薇儿就身患该种疾病。

患上莱姆症最初会出现皮肤红疹及类似感冒的症状，因此很容易误诊，目前的标准诊断方法是检测感染后积累的病原体抗原。近期一组科学家们利用白细胞中的一种特殊基因转录模式，研发出了新型莱姆症诊断方法，这要比目前的技术能更早的发现这种疾病。这一研究成果公布在2月12日的mBio杂志上。

“改进后的诊断方法能用于莱姆症急诊所需，”文章作者，加州大学旧金山分校Charles Chiu说，“传染莱姆症的蜱虫也会传播许多其它的病原体，早期诊断是指导进行适当的治疗和预防疾病后期并发症的关键所在。”

Chiu等人利用RNA测序，检测了29位患者在服用三周抗生素治疗之前和之后的血液样品，发现了独特的莱姆症相关基因信号。并且在六个月后再次检测患者的血样时，研究人员发现这一转录组中部分序列依然存在。

“就我们所知，这是首个记录细菌感染进行抗生素治疗后发生基因表达变化的研究，”文章作者，约翰霍普金斯医学院莱姆病临床研究中心主任John Aucott说。

与此同时，研究人员也发现B. burgdorferi 膜蛋白检测可以作为另外一种可行的诊断技术。

“我们认为莱姆细菌会从细胞壁中衍生出囊泡状微粒或片段，这种微粒中包含有膜蛋白，可以作为独特的感染指标，”另外一位作者Larik Turko说，“从这许多候选中，我们选择了ospA，因为ospA易于与人体内其它血清蛋白区分开来，也可以作为细菌的一个明确指标。”

经过实验验证，一位未确诊莱姆症的患者利用这种转录组技术能在标准检测方法确诊之前三周，就能检测到细菌，而同时另外一项发表在 Analytical Chemistry杂志上的文章指出，另外两位患者也能利用新技术同时检测出感染来。

“莱姆症本身的复杂性，同时加上缺乏检测感染的生物标志物，会延缓疾病的治疗进程，”Aucott说，“现在，随着新技术的发展，我们能用最小浓度的血液分子，检测出这种疾病了。”

（生物通：张迪）

原文摘要：

Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets.