Ueland Thor, Rollag Halvor, Hartmann Anders, Jardine Alan, Humar Atul, Bignamini Angelo A, Åsberg Anders, Aukrust Pål
1 Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2 Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 3 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4 Department of Organ Transplantation, Gastroenterology and Nephrology, Section for Nephrology, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway. 5 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 6 Faculty of Medicine, University of Oslo, Oslo, Norway. 7 K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway. 8 Institute of Cardiovascular and Medical Sciences University of Glasgow, Glasgow, United Kingdom. 9 Department of Medicine, University of Alberta, Edmonton, Canada. 10 School of Specialization in Hospital Pharmacy, University of Milan, Milan, Italy.
Transplantation. 2015 Jan;99(1):100-5. doi: 10.1097/TP.0000000000000227.
Cytomegalovirus (CMV) infection involves interaction between endothelial cells and leukocyte subsets that may promote vascular inflammation and lead to treatment failure in infected individuals. Osteoprotegerin is a marker of vascular and systemic inflammation but has not been investigated in relation to treatment outcome during CMV infection.
We investigated whether circulating levels of osteoprotegerin are related to features of CMV disease and treatment outcomes during CMV infection in 291 solid organ transplant recipients receiving valganciclovir or ganciclovir in an international multicenter trial of CMV disease treatment (the VICTOR study).
Elevated plasma osteoprotegerin was associated with (i) certain disease characteristics including presence of tissue invasive disease (P<0.05) and increased viral load at baseline (P<0.05), (ii) poor virological outcome at day 49 after anti-CMV therapy, (iii) increased plasma levels of markers of inflammation (pentraxin 3 and C-reactive protein) and endothelial cell activation (von Willebrand factor) both at baseline and during follow-up.
Our finding indicates that elevated osteoprotegerin levels in solid organ transplant recipients with CMV infection may reflect vascular inflammation and is associated with late virological outcome in these patients.
巨细胞病毒（CMV）感染涉及内皮细胞与白细胞亚群之间的相互作用，这可能会促进血管炎症，并导致感染个体的治疗失败。骨保护素是血管和全身炎症的标志物，但尚未针对CMV感染期间的治疗结果进行研究。
在一项CMV疾病治疗的国际多中心试验（VICTOR研究）中，我们调查了291名接受缬更昔洛韦或更昔洛韦治疗的实体器官移植受者中，骨保护素的循环水平是否与CMV疾病的特征及治疗结果相关。
血浆骨保护素升高与以下情况相关：（i）某些疾病特征，包括组织侵袭性疾病的存在（P<0.05）和基线时病毒载量增加（P<0.05）；（ii）抗CMV治疗后第49天病毒学结果不佳；（iii）基线和随访期间炎症标志物（五聚素3和C反应蛋白）及内皮细胞激活标志物（血管性血友病因子）的血浆水平升高。
我们的研究结果表明，CMV感染的实体器官移植受者骨保护素水平升高可能反映血管炎症，并与这些患者的晚期病毒学结果相关。
