Human mast cells present antigen to autologous CD4+ T cells

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Criteria to define interruption of transmission of human cytomegalovirus from organ donor to recipient

In this review article, we consider results suggesting that transmission of human cytomegalovirus (HCMV) from a donor of a solid organ to an immunologically naive individual can be reduced. Two randomized controlled trials have been conducted recently, one of active immunization of recipients pretransplant and another of passive immunization with monoclonal antibodies specific for HCMV given at the time of transplant. Although the available data are encouraging—providing evidence of a reduction in the incidence of HCMV viraemia—they fall short of what would be required to prove definitively that transmission has been completely prevented. Here, we reflect on these studies and propose a set of 5 criteria, which, if satisfied in the future, could be taken as proof that active and/or passive immunization against HCMV effectively interrupts transmission of virus from the donor. We suggest that these criteria are considered when designing future randomized controlled trials.     

Antiphospholipid syndrome: An update on risk factors for pregnancy outcome

Background

The optimal treatment of women with primary antiphospholipid syndrome (APS) is still debated. About 20–30% of women with APS remain unable to give birth to healthy neonates despite conventional treatment, consisting of prophylactic-dose heparin and low-dose aspirin. These cases are defined “refractory obstetric APS”. The early identification of risk factors associated with poor pregnancy outcome could be the optimal strategy to establish criteria for additional therapies, such as hydroxychloroquine, steroids, intravenous immunoglobulin, and plasma exchange.

The incidence of chylous ascites after liver transplantation and the proposal of a diagnostic and management protocol

Background

No protocol has been established for the diagnosis and management of chylous ascites after liver transplantation (LT). In this study, we retrospectively reviewed our cases of posttransplant chylous ascites (PTCA) and aimed to propose a diagnostic and management protocol.

The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells

It has been reported that atherosclerotic lesions contain genomic material belonging to members of the herpes family. This suggests that latent viral infection may be one of the atherogenic triggers. In this study we show that early infection of endothelial cell monolayers with Herpes Simplex virus type 1 (HSV-1) or Cytomegalovirus (CMV) results in an increased monocyte (MC) and polymorphonuclear leukocyte (PMN) adherence, but not in an increased platelet adhesion. Further, is demonstrated that MC and PMN respond differently to virus infected endothelial cell monolayers: PMN adhesion to CMV infected cells is approximately 430% of the control adherence, while the MC adherence is increased to 160%. Also, a difference in virus acting is observed: the adherence of MC or PMN to HSV-1 infected endothelial cells is caused by a secreted adherence promoting factor, while the adherence of MC or PMN to CMV infected endothelial cells seems to be a cell-bound phenomenon. In addition, it was demonstrated that the augmentation of MC or PMN adherence to virus infected endothelial cells is sensitive to tunicamycin, suggesting that both virus infections induce the expression of glycoproteins on the endothelial cell membrane, which is responsible for the MC and PMN adhesion. Thus, HSV-1 and CMV infection of endothelium results in an increased adherence of leukocytes which is suggested, irrespective of the precise nature of the mechanism of virus induced atherosclerosis, to be the earliest event associated with endothelium cell damage.     

器官移植受者微量CMV DNA与IL-10基因单核苷酸多态性的相关性研究

目的研究白介素-10（IL-10）基因G1082A和C819T单核苷酸多态性（SNP）与移植术后外周血微量巨细胞病毒（CMV）DNA的关系。万法采集176例移植术后受者，429例次的外周血。通过巢式聚合酶链反应（nPcR）技术检测微量CMV DNA。通过序列特异性聚合酶链反应（SSP-PCR）技术检测IL-10基因G1082A与C819T的变异情况。分析IL-10各基因型在微量CMV DNA受者中的分布频率，并对阳性组与阴性组进行比较。结果研究人群中IL-10 G1082A和C819T基因型分布符合Hardy-Weinberg遗传平衡定律。CMV DNA阳性组IL-10 G1082A和C819T等位基因频率分别为G=3.75％、A=96.25％和C=32.50％、T=67.50％；CMV DNA阴性组分别为G=5.51％、A=94.49％和C=36.03％、T=63.97％。CMV DNA阳性组两SNP基因型及等位基因分布与其在CMV DNA阴性组中的分布差异无显著性（P〉0.05）。结论目前尚不能认为IL-10基因G1082A与C819T单核苷酸多态性与移植受者微量CMV DNA阳性有相关性。     

大蒜新素体内外抑制小鼠巨细胞病毒感染诱导的调节性T细胞扩增实验研究

目的 在体内外水平研究大蒜新素对小鼠巨细胞病毒 (murine cytomegalovirus, MCMV) 感染导致调节性 T 细胞 (regulatory T cells, Treg) 异常扩增的抑制作用。方法 72 只 MCMV 感染小鼠随机分为安慰剂组和大蒜新素治疗组;并设 72 只同期模拟感染小鼠为对照,随机分为模拟感染对照组和大蒜新素对照组。分别于大蒜新素处理后 1、7、14、28、60、120 d 处死小鼠,获得脾细胞待测。采用 Western blotting 法检测脾细胞中 Foxp3 的蛋白表达强度;流式细胞术分析 CD4+CD25+Foxp3+Treg 细胞在脾细胞中所占比率的变化。采用小鼠胚胎成纤维细胞对大蒜新素的最大耐受浓度处理 MCMV 感染的胚胎成纤维细胞 3 d 后,采用 Realtime PCR 法和 Western blotting 法分别检测 T 细胞中 Foxp3 mRNA 和蛋白的表达水平。结果 整体研究发现,大蒜新素对正常小鼠脾细胞中 Foxp3 蛋白表达和 Treg 细胞比率均无显著影响;但是在 MCMV 感染小鼠,大蒜新素可在感染慢性期显著减少 Foxp3 蛋白表达强度、降低调节性 T 细胞比率。体外细胞模型发现,最大耐受浓度的大蒜新素加入共培养体系后可部分拮抗 MCMV 诱导的 Foxp3 基因和蛋白表达上调。结论 大蒜新素在体内外均可显著纠正 MCMV 感染导致的 Treg 异常扩增。大蒜新素通过影响 Treg 增殖进而增强抗病毒免疫而有利于机体清除 CMV 病毒,可能是大蒜新素诱导抗 CMV 免疫的另一重要机制。     

High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for adult T cell leukemia

The etiology of cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) reactivation and the potential for complications following cytotoxic chemotherapy in the absence of allogeneic transplantation are not clearly understood. Patients with adult T cell leukemia (ATL) are susceptible to opportunistic infections. In this study, the incidence, kinetics and clinical significance of reactivation of CMV, HHV-6, and EBV in ATL patients were investigated. Viral DNA in a total of 468 plasma samples from 34 patients was quantified using real-time PCR. The probability of CMV, HHV-6, and EBV reactivation by 100 days after the start of chemotherapy was 50.6%, 52.3%, and 21.6%, respectively. Although most CMV reactivations were self-limited, plasma CMV DNA tended to persist or increase if the CMV DNA levels in plasma reached ≥ 10(4) copies/ml. CMV reactivation was negatively associated with survival, but the P-value for this association was near the borderline of statistical significance (P=0.052). One patient developed fatal interstitial pneumonia concomitant with peak CMV DNA accumulation (1.6 × 10(6) copies/ml plasma). Most HHV-6 and EBV reactivations were self-limited, and no disease resulting from HHV-6 or EBV was confirmed. HHV-6 and EBV reactivation were not associated with reduced survival (P=0.35 and 0.11, respectively). These findings demonstrated that subclinical reactivation of CMV, HHV-6, and EBV were common in ATL patients receiving chemotherapy. There were differences in the viral reactivation patterns among the three viruses. A CMV load ≥ 10(4) copies/ml plasma was indicative of subsequent exacerbation of CMV reactivation and developing serious clinical course.