Jansen Anne F M, Schoffelen Teske, Textoris Julien, Mege Jean-Louis, Nabuurs-Franssen Marrigje, Raijmakers Ruud P H, Netea Mihai G, Joosten Leo A B, Bleeker-Rovers Chantal P, van Deuren Marcel
Department of Internal Medicine 463, Radboud center for Infectious Diseases (RCI), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Radboud Expert Center for Q fever, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
BMC Infect Dis. 2017 Aug 9;17(1):556. doi: 10.1186/s12879-017-2656-6.
In the aftermath of the largest Q fever outbreak in the world, diagnosing the potentially lethal complication chronic Q fever remains challenging. PCR, Coxiella burnetii IgG phase I antibodies, CRP and F-FDG-PET/CT scan are used for diagnosis and monitoring in clinical practice. We aimed to identify and test biomarkers in order to improve discriminative power of the diagnostic tests and monitoring of chronic Q fever.
We performed a transcriptome analysis on C. burnetii stimulated PBMCs of 4 healthy controls and 6 chronic Q fever patients and identified genes that were most differentially expressed. The gene products were determined using Luminex technology in whole blood samples stimulated with heat-killed C. burnetii and serum samples from chronic Q fever patients and control subjects.
Gene expression of the chemokines CXCL9, CXCL10, CXCL11 and CCL8 was strongly up-regulated in C. burnetii stimulated PBMCs of chronic Q fever patients, in contrast to healthy controls. In whole blood cultures of chronic Q fever patients, production of all four chemokines was increased upon C. burnetii stimulation, but also healthy controls and past Q fever individuals showed increased production of CXCL9, CXCL10 and CCL8. However, CXCL9 and CXCL11 production was significantly higher for chronic Q fever patients compared to past Q fever individuals. In addition, CXCL9 serum concentrations in chronic Q fever patients were higher than in past Q fever individuals.
CXCL9 protein, measured in serum or as C. burnetii stimulated production, is a promising biomarker for the diagnosis of chronic Q fever.
在全球最大规模的Q热疫情爆发之后，诊断具有潜在致命性的并发症——慢性Q热仍然具有挑战性。在临床实践中，聚合酶链反应（PCR）、伯氏考克斯体IgG Ⅰ相抗体、C反应蛋白（CRP）和氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（F-FDG-PET/CT）用于诊断和监测。我们旨在识别和测试生物标志物，以提高诊断测试对慢性Q热的鉴别能力和监测水平。
我们对4名健康对照者和6名慢性Q热患者经伯氏考克斯体刺激的外周血单核细胞（PBMC）进行了转录组分析，并确定了差异表达最明显的基因。使用Luminex技术在经热灭活的伯氏考克斯体刺激的全血样本以及慢性Q热患者和对照者的血清样本中测定基因产物。
与健康对照者相比，慢性Q热患者经伯氏考克斯体刺激的PBMC中趋化因子CXCL9、CXCL10、CXCL11和CCL8的基因表达强烈上调。在慢性Q热患者的全血培养物中，经伯氏考克斯体刺激后所有四种趋化因子的产生均增加，但健康对照者和既往感染Q热者CXCL9、CXCL10和CCL8的产生也增加。然而，与既往感染Q热者相比，慢性Q热患者CXCL9和CXCL11的产生明显更高。此外，慢性Q热患者的CXCL9血清浓度高于既往感染Q热者。
血清中检测到的CXCL9蛋白或作为经伯氏考克斯体刺激产生的蛋白，是诊断慢性Q热的一种有前景的生物标志物。
