Das Bibhuti B, Prusty Bhupesh K, Niu Jianli, Huang Meei-Li, Zhu Haiying, Eliassen Eva, Kuypers Jane M, Jerome Keith R
Department of Pediatrics, Division of Pediatric Cardiology, Baylor College of Medicine, Texas Children's Hospital, Austin, Texas, USA.
Department of Microbiology, Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Ann Pediatr Cardiol. 2020 Oct-Dec;13(4):301-308. doi: 10.4103/apc.APC_124_19. Epub 2020 Sep 1.
The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (IFA) in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral persistence in the cardiac allograft after heart transplantation (HT).
Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial samples from 48 pediatric DCM patients and 10 control subjects. Of the 48 DCM patients, 44 underwent HT. After HT, consecutive endomyocardial biopsy (EMB) samples were analyzed for the presence of PVB19 and HHV-6 antigens using IFA and the patients were evaluated for rejections, coronary vasculopathy, and graft loss.
Of the 48 DCM patients, 14 had positive viral PCR results in explanted/autopsy hearts. Among them, PVB19 was found in 8/48, HHV6 in 4/48, both PVB19 and HHV6 in 1/48, and enterovirus in one, but no adenovirus was found. The EMB samples obtained after HT were positive for PVB19 and HHV-6 in 7/44 and 3/44 cases, respectively. Viral presence in both the explanted heart and the cardiac allograft was demonstrated in 4 patients, 3 of whom were positive for PVB19, and one of whom was positive for HHV-6 pretransplant. Coronary vasculopathy and graft loss were more common in patients with PVB19-positive myocardial tissues versus those who were PVB19-negative.
There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.
本研究旨在采用聚合酶链反应(PCR)和免疫荧光测定法(IFA)评估扩张型心肌病(DCM)患儿心肌中的人疱疹病毒6型(HHV-6)和细小病毒B19(PVB19)感染情况,以及心脏移植(HT)后病毒持续存在对心脏移植受者的影响。
采用多重液滴数字PCR分析48例小儿扩张型心肌病患者和10例对照者心肌样本中病毒序列的流行情况。48例DCM患者中,44例接受了心脏移植。心脏移植后,连续的心内膜心肌活检(EMB)样本采用IFA分析PVB19和HHV-6抗原的存在情况,并对患者进行排斥反应、冠状动脉血管病变和移植物丢失的评估。
48例DCM患者中,14例在移植心脏/尸检心脏中病毒PCR结果呈阳性。其中,48例中有8例发现PVB19,48例中有4例发现HHV6,48例中有1例同时发现PVB19和HHV6,1例发现肠道病毒,但未发现腺病毒。心脏移植后获得的EMB样本中,44例中有7例PVB19呈阳性,44例中有3例HHV-6呈阳性。4例患者的移植心脏和心脏移植物中均检测到病毒,其中3例PVB19呈阳性,1例移植前HHV-6呈阳性。与PVB19阴性的患者相比,PVB19阳性心肌组织的患者冠状动脉血管病变和移植物丢失更为常见。
儿童PVB19和HHV-6感染与扩张型心肌病之间存在关联。该研究表明,即使在没有活动性心肌炎的受者中,宿主中PVB19和HHV-6的持续存在也可能导致移植心脏中随后的病毒再激活。心脏移植物中的PVB19往往会导致更高的心脏移植后不良事件发生率。