Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation
Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation
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DOI：
10.1016/j.healun.2009.12.013
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发表时间：
2010-06-01
影响因子：
8.9
通讯作者：
van den Bosch, Jules M. M.
中科院分区：
文献类型：
--
作者：
Kastelijn, Elisabeth A.;van Moorsel, Coline H. M.;van den Bosch, Jules M. M.
背景：免疫系统的激活被认为可以防止移植耐受并促进闭塞性细支气管炎综合征（BOS）的发展。先天免疫系统是通过微生物病原体相关分子模式与 Toll 样受体 (TLR) 的相互作用来激活的。通过 TLR 激活先天免疫被证明是肺移植后诱导移植耐受的障碍。我们假设编码 TLR1 至 TLR1 0 的 10 个基因的多态性可能会导致免疫反应的改变以及 BOS 的后续发展。方法：从 110 名肺移植受者身上收集 DNA。 20 名患者出现 BOS。对照组由 422 人组成。对编码 TLR10 至 TLR10 的 10 个基因中的 64 个单核苷酸多态性（SNP）进行了基因分型。结果：TLR2（rs1898830 和 rs7656411）、TLR4（rs1927911）和 TLR9（rs352162 和 rs187084）的基因型分布在 BOSpos 患者和 BOSpos 患者之间存在显着差异。 BOSneg 患者和对照。与 BOSneg 组和对照组相比，BOSpos 组携带 3 或 4 个这些风险等位基因的患者明显更多。结论：识别细菌和病毒病原体的 TLR2、TLR4 和 TLR9 多态性与肺移植后的 BOS 相关。 J Heart Lung Transplant 2010；29:665-71 (C) 2010 国际心肺移植学会。版权所有。
BACKGROUND: Activation of the immune system is suggested to prevent transplant tolerance and to promote the development of bronchiolitis obliterans syndrome (BOS). The innate immune system is activated by the interaction of pathogen-associated molecular patterns of microorganisms with Toll-like receptors (TLRs). Activation of innate immunity via TLRs was shown to be a barrier to the induction of transplantation tolerance after lung transplantation. We hypothesized that polymorphisms in 10 genes coding for TLR1 to TLR1 0 might contribute to an altered immune response and the subsequent development of BOS.METHODS: DNA was collected from 110 lung transplant recipients. Twenty patients developed BOS. The control group comprised 422 individuals. Sixty-four single-nucleotide polymorphisms (SNPs) in 10 genes coding for TLR10 to TLR10 were genotyped.RESULTS: The genotype distribution of TLR2 (rs1898830 and rs7656411), TLR4 (rs1927911) and TLR9 (rs352162 and rs187084) was significantly different between BOSpos patients and BOSneg patients and controls. The BOSpos group had significantly more patients with 3 or 4 of these risk alleles compared with the BOSneg and control groups.CONCLUSIONS: Polymorphisms in TLR2, TLR4 and TLR9 that recognize bacterial and viral pathogens are associated with BOS after lung transplantation. J Heart Lung Transplant 2010;29:665-71 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved.