Badawi Alaa, Arora Paul, Brenner Darren
Public Health Risk Sciences Division, Public Health Agency of Canada, Toronto, Canada.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
Infect Dis Ther. 2019 Mar;8(1):5-22. doi: 10.1007/s40121-018-0223-0. Epub 2018 Nov 30.
Lyme disease-also known as Lyme borreliosis (LB)-is the most common vector-borne disease in North America and Europe. It may result in substantial morbidity, primarily from persistent Lyme arthritis (LA) that-although treatable-can develop into antibiotic-refractory LA (A-RLA). The aim of this study is to systematically review and evaluate a range of biomarkers for their potential predictive value in the development of A-RLA.
We conducted a systematic review of studies examining biomarkers among patients with A-RLA from MEDLINE via OVID, EMBASE and Web of Science databases and identified a total of 26 studies for qualitative analysis.
All studies were of patient populations from the USA, with the exception of one from Europe. We identified an array of biomarkers that are commonly modulated in the A-RLA compared with subjects with antibiotic-responsive LA. These included a range of inflammatory markers (IL-6, IL-8, IL-10, IL-1β, IL-23, IL-17F, TNFα, IFNγ, CXCL9, CXCL10, CCL2, CCL3 and CCL4, CRP), factors along the innate and adaptive immune response pathways (e.g., CD4 T cells, GITR receptors, OX40 receptors, IL-4CD4Th2 cells, IL-17CD4 T cells) and an array of miRNA species (e.g., miR-142, miR-17, miR-20a, let-7c and miR-30fam).
The evidence base of biologic markers for A-RLA is limited. However, a range of promising biomarkers have been identified. Cytokines and chemokines related to Th17 pathway together with a number of miRNAs species (miR-146a, miR-155 and let-7a) may be promising candidates in the prediction of A-RLA. A panel of multiple biomarkers may yield clinically relevant prediction of the possible resistance at the time of LA first diagnosis.
Public Health Agency of Canada.
莱姆病，也称为莱姆疏螺旋体病（LB），是北美和欧洲最常见的媒介传播疾病。它可能导致严重的发病率，主要源于持续性莱姆关节炎（LA），尽管这种关节炎可以治疗，但可能发展为抗生素难治性莱姆关节炎（A-RLA）。本研究的目的是系统评价和评估一系列生物标志物在A-RLA发生发展中的潜在预测价值。
我们通过OVID对MEDLINE、EMBASE和科学引文索引数据库中有关A-RLA患者生物标志物的研究进行了系统评价，共确定26项研究进行定性分析。
除一项来自欧洲的研究外，所有研究的患者群体均来自美国。我们确定了一系列与抗生素反应性莱姆关节炎患者相比在A-RLA中通常受到调节的生物标志物。这些包括一系列炎症标志物（白细胞介素-6、白细胞介素-8、白细胞介素-10、白细胞介素-1β、白细胞介素-23、白细胞介素-17F、肿瘤坏死因子α、干扰素γ、CXC趋化因子配体9、CXC趋化因子配体10、CC趋化因子配体2、CC趋化因子配体3和CC趋化因子配体4、C反应蛋白）、先天和适应性免疫反应途径中的因子（如CD4 T细胞、糖皮质激素诱导的肿瘤坏死因子受体、OX40受体、白细胞介素-4 CD4辅助性T细胞2型、白细胞介素-17 CD4 T细胞）以及一系列微小RNA种类（如微小RNA-142、微小RNA-17、微小RNA-20a、微小RNA-7c和微小RNA-30家族）。
A-RLA生物标志物的证据基础有限。然而，已经确定了一系列有前景的生物标志物。与辅助性T细胞17途径相关的细胞因子和趋化因子以及一些微小RNA种类（微小RNA-146a、微小RNA-155和微小RNA-7a）可能是预测A-RLA的有前景的候选物。一组多种生物标志物可能在莱姆关节炎首次诊断时对可能的耐药性产生临床相关的预测。
加拿大公共卫生局。
