Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection
Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection
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DOI：
10.1097/01.tp.0000250579.08042.b6
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发表时间：
2007-01-27
期刊：
影响因子：
6.2
通讯作者：
Mohanakumar, Thalachallour
中科院分区：
文献类型：
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作者：
Bharat, Ankit;Narayanan, Kishore;Mohanakumar, Thalachallour
背景以闭塞性细支气管炎综合征（BOS）为代表的慢性肺移植排斥反应是限制肺移植（LT）后长期生存的最重要因素。然而，BOS的发病机制仍不清楚。我们假设移植后早期炎症反应会促进供体抗人类白细胞抗原（HLA）同种免疫的发展，并使其易患BOS。白细胞介素（IL）-1 β、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12、IL-13、IL-15、IL-17、嗜酸性粒细胞趋化因子、IP-10、IL-14、MCP-1、MIP-1 α、MIP-1 β、RANTES、肿瘤坏死因子（TNF）-α、干扰素（IFN）-α、IFN-γ、粒细胞-巨噬细胞集落刺激因子、IL-1 R α、采用多重免疫磁珠定量分析法对31例BOS+和31例BOS-患者进行了IL-2和IL-2 R的系列分析。使用酶联免疫斑点（ELISPOT）通过检测受体外周血单个核细胞对不匹配的供体HLA-DR肽的反应来分析供体特异性HLA 11类细胞免疫。用流式细胞仪检测抗HLA 11类抗体。与BOS-和正常受试者相比，BOS+患者的促炎趋化因子IP-10和MCP-1以及Th 1细胞因子IL-10、IL-2、IL-12和IL-15的基础血清水平在移植后早期升高。此外，在BOS发展过程中发现IL-10水平下降三倍。BOS+患者显示HLA II类同种抗体和Th 1占主导地位的供者特异性细胞免疫的发展增加，IFN-γ和低IL-5产生的T细胞的频率高。移植后早期促炎介质升高与同种异体免疫和慢性人肺移植排斥反应有关。
Background. Chronic human lung allograft rejection, represented by bronchiolitis obliterans syndrome (BOS), is the single most important factor that limits the long-term survival following lung transplantation (LT). However, the pathogenesis of BOS remains unclear. We hypothesized that the early posttransplant inflammation would promote the development of donor anti-human leukocyte antigen (HLA) alloimmunity and predispose to BOS.Methods. Serum levels of interleukin (IL)-1 beta IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, IP-10, MIG, MCP-1, MIP-1 alpha, MIP-1 beta, RANTES, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony- stimulating factor, IL-IR alpha, and IL-2R were serially analyzed in 31 BOS+ and matched 31 BOS- patients using quantitative multiplex bead immunoassays. Donor-specific HLA class 11 cellular immunity was analyzed using enzyme-linked immunospot (ELISPOT) by testing recipient peripheral blood mononuclear cells against mismatched donor HLA-DR pepticles. Anti-HLA class 11 antibodies were monitored using flow panel reactive antibodies.Results. There was early posttransplant elevation in basal serum levels of proinflammatory chemokines IP-10 and MCP-1 and Th1-cytokines IL-10, IL-2, IL-12, and IL-15 in BOS+ patients, compared to BOS- and normal subjects. In addition, a threefold decline in IL-10 levels was found during BOS development. BOS+ patients revealed increased development of HLA class II alloantibodies and Th1-predominant donor-specific cellular immunity with high frequency of IFN-gamma and low IL-5 producing T-cells.Conclusion. Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.