Norton Thoracic Institute, St Joseph's Hospital and Medical Center, Phoenix, Ariz.
Norton Thoracic Institute, St Joseph's Hospital and Medical Center, Phoenix, Ariz.
J Thorac Cardiovasc Surg. 2019 May;157(5):2096-2106. doi: 10.1016/j.jtcvs.2018.12.105. Epub 2019 Feb 12.
Lung transplantation is therapeutic for end-stage lung disease, but survival is limited due to bronchiolitis obliterans syndrome and restrictive chronic lung allograft dysfunction. We sought a common denominator in lung transplant recipients, analyzing risk factors that trigger immune responses that lead to bronchiolitis obliterans syndrome.
We collected blood from patients who underwent lung transplant at our institution. Exosomes were isolated from the sera of recipients with risk factors for chronic rejection and from stable recipients. Exosomes were analyzed with western blot, using antibodies to lung self-antigens K alpha 1 tubulin and collagen-V, costimulatory molecules (costimulatory molecule 80, costimulatory molecule 86), transcription factors (nuclear factor kappa-light-chain-enhancer of activated B cells, hypoxia-inducible factor 1α, Class II Major Histocompatibility Complex Transactivator), and 20S proteasome.
Of the 90 patients included, we identified 5 with grade 3 primary graft dysfunction, 5 without, 15 with respiratory viral infection, 10 with acute rejection, 10 with donor-specific antibodies (DSA), 5 without DSA, and 10 who were stable for exosome isolation. Recipients with grade 3 primary graft dysfunction, respiratory viral infection, acute rejection, and DSA had exosomes containing self-antigens; exosomes from stable recipients did not. Exosomes from recipients with grade 3 primary graft dysfunction, acute rejection, and DSA also demonstrated costimulatory molecule 80, costimulatory molecule 86, major histocompatibility complex class II, transcription factor, and 20S proteasome.
Transplanted lungs with grade 3 primary graft dysfunction, symptomatic respiratory viral infection, acute rejection, and immune responses induce exosomes that contain self-antigens, costimulatory molecules, major histocompatibility complex class II, transcription factors, and 20S proteasome. Release of circulating exosomes post-transplant from the aforementioned stress-inducing insults augment immunity and may play an important role in the pathogenesis of bronchiolitis obliterans syndrome.
肺移植是治疗终末期肺部疾病的一种方法，但由于闭塞性细支气管炎综合征和限制性慢性肺移植物功能障碍，其存活率有限。我们试图找到肺移植受者的共同特征，分析触发导致闭塞性细支气管炎综合征免疫反应的危险因素。
我们收集了在我们机构接受肺移植的患者的血液。从有慢性排斥反应风险因素的受者和稳定受者的血清中分离出外泌体。使用针对肺自身抗原 Kα1 微管蛋白和胶原-V、共刺激分子（共刺激分子 80、共刺激分子 86）、转录因子（核因子 kappa 轻链增强子的激活 B 细胞、缺氧诱导因子 1α、II 类主要组织相容性复合物反式激活因子）和 20S 蛋白酶体的抗体，对分离的外泌体进行 Western blot 分析。
在 90 例患者中，我们发现 5 例有 3 级原发性移植物功能障碍，5 例无 3 级原发性移植物功能障碍，15 例有呼吸道病毒感染，10 例有急性排斥反应，10 例有供体特异性抗体（DSA），5 例无 DSA，10 例稳定用于外泌体分离。有 3 级原发性移植物功能障碍、呼吸道病毒感染、急性排斥反应和 DSA 的受者的外泌体含有自身抗原；而稳定受者的外泌体则没有。有 3 级原发性移植物功能障碍、急性排斥反应和 DSA 的受者的外泌体还显示出共刺激分子 80、共刺激分子 86、主要组织相容性复合物 II、转录因子和 20S 蛋白酶体。
3 级原发性移植物功能障碍、有症状的呼吸道病毒感染、急性排斥反应和免疫反应的移植肺会诱导含有自身抗原、共刺激分子、主要组织相容性复合物 II、转录因子和 20S 蛋白酶体的外泌体。移植后，来自上述应激诱导损伤的循环外泌体的释放会增强免疫反应，并可能在闭塞性细支气管炎综合征的发病机制中发挥重要作用。
