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肺移植中病毒感染的最新进展。

Update on viral infections in lung transplantation.

机构信息

Center for Allogeneic Stem Cell Transplantation, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Curr Opin Pulm Med. 2012 May;18(3):264-70. doi: 10.1097/MCP.0b013e3283521066.

Abstract

PURPOSE OF REVIEW

Lung transplantation is an established therapeutic option for patients with severe respiratory insufficiency. Graft dysfunction or rejection depends on the orchestrated prevention of infection(s) and the level of immune suppression. More recent reports underlined the role and pathogenicity of cytomegalovirus (CMV) infection in lung transplant recipients and the double-edged sword of maintaining antiviral immune responses versus guided immune suppression to avoid graft rejection. We present data concerning the nature of the cellular response to Epstein-Barr virus (EBV) and CMV, the subsequent use of cellular therapy in antiviral treatment modalities and discuss the role of H1N1 infection and other viral infections in lung transplantation recipients.

RECENT FINDINGS

Patients after lung transplantation showed a similar susceptibility to H1N1 infections as compared to the local, healthy community. After initial recovery and oseltamivir treatment, lung transplantation patients developed bronchiolitis obliterans syndrome. The genetic background of lung transplant recipients, defined by polymorphism in immune molecules, contributes to increased risk of CMV disease; CMV induces local pro-inflammatory chemokines (CXCL10). Anti-CMV prophylaxis does not impact on anti-CMV-directed cellular immune responses, defined by IFNγ and TNFα production. Asymptomatic EBV carriers showed higher numbers of EBV-reactive T cells. High EBV load carriers showed T cells with immune-exhaustion markers and decreased IFNγ production. Anti-CMV-directed cellular therapy may aid to better manage CMV-associated complications after lung transplantation.

SUMMARY

Pharmacological immune suppression, the genetic makeup of the patient as well as concurrent viral infections impact on the successful outcome of lung transplantation and call for more detailed immune-guided diagnostics and therapy.

摘要

目的综述

肺移植是治疗严重呼吸功能不全患者的一种成熟的治疗方法。移植物功能障碍或排斥取决于感染的协调预防和免疫抑制水平。最近的报告强调了巨细胞病毒(CMV)感染在肺移植受者中的作用和致病性,以及维持抗病毒免疫反应与指导免疫抑制以避免移植物排斥之间的双刃剑。我们介绍了有关细胞对 EBV 和 CMV 反应的性质、细胞治疗在抗病毒治疗方式中的后续应用的数据,并讨论了 H1N1 感染和其他病毒感染在肺移植受者中的作用。

最新发现

肺移植后患者与当地健康人群相比,对 H1N1 感染的易感性相似。在初始恢复和奥司他韦治疗后,肺移植患者发生了闭塞性细支气管炎综合征。肺移植受者的遗传背景,由免疫分子的多态性定义,增加了 CMV 疾病的风险;CMV 诱导局部促炎趋化因子(CXCL10)。抗 CMV 预防并不影响 IFNγ 和 TNFα产生的抗 CMV 定向细胞免疫反应。无症状 EBV 携带者表现出更高数量的 EBV 反应性 T 细胞。高 EBV 负荷携带者表现出具有免疫衰竭标志物的 T 细胞和减少的 IFNγ 产生。抗 CMV 定向细胞治疗可能有助于更好地管理肺移植后与 CMV 相关的并发症。

总结

药物免疫抑制、患者的遗传构成以及并发的病毒感染都会影响肺移植的成功结果,需要更详细的免疫指导诊断和治疗。

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