Sharma Monal, Ravichandran Ranjithkumar, Bansal Sandhya, Bremner Ross M, Smith Michael A, Mohanakumar T
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Hum Immunol. 2018 Sep;79(9):653-658. doi: 10.1016/j.humimm.2018.06.005. Epub 2018 Jun 15.
Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection.
外泌体是表达自身抗原（SAgs）和供体人类白细胞抗原的细胞外囊泡。在肺、心脏、肾脏和胰岛细胞移植后，可在循环系统中检测到组织特异性外泌体。我们收集了接受肺移植（n = 30）、心脏移植（n = 8）或肾脏移植（n = 15）患者的血清样本，以分离循环外泌体。使用CD9外泌体特异性标志物通过蛋白质印迹法分析外泌体纯度。使用蛋白质印迹法鉴定了组织相关的肺SAgs、胶原蛋白V（Col-V）和K-α1微管蛋白（Kα1T）、心脏SAgs、肌球蛋白和波形蛋白，以及肾脏SAgs、纤连蛋白和胶原蛋白IV（Col-IV）。诊断为闭塞性细支气管炎综合征的肺移植受者的外泌体中Col-V（4.2倍）和Kα1T（37.1倍）的表达高于病情稳定者。与病情稳定者相比，从诊断为冠状动脉血管病的心脏移植受者中分离的外泌体中肌球蛋白增加了3.9倍，波形蛋白增加了4.7倍。此外，诊断为移植性肾小球病的肾脏移植受者的循环外泌体中纤连蛋白表达增加了2倍，Col-IV增加了2.5倍。我们得出结论，携带组织相关SAgs的循环外泌体有可能成为同种异体移植排斥反应的非侵入性生物标志物。
