The relationship between anti-donor antibodies and acute rejection in lung transplantation

在本研究中，我们试图通过流式细胞术检测抗供体抗体来诊断大鼠肺移植急性排斥反应的可能性。在轻度排斥时，移植后2天外周血中循环的特异性同种异体抗体已经显著增加，而直到移植后6.4天和6天移植物中没有明显的同种异体抗体沉积，此时血液中IgM抗体的升高比IgG抗体的升高更明显。第8天，免疫球蛋白抗体持续升高。而IgM抗体在术后第6天显著下降。结论：在同种异体移植物发生轻度排斥反应(A2)时，FCM可检测到外周血中循环的抗供体抗体，有趣的是，这些抗体在移植物中明显沉积之前即可被检测到。我们还试图通过检测环孢素A处理的大鼠肺移植模型的外周血中的抗供体抗体来验证诊断急性排斥反应的可能性。移植后第4天的病理结果被分为A2级，A2或A3级的第8天和12天，A3或A4级的第16天。供体特异性IgM抗体在移植后第4天开始升高，第8天开始下降，而免疫球蛋白抗体水平在第8天开始升高，并在整个观察期内持续升高。结论：FCM检测外周血中抗供体IgM抗体有助于早期发现急性排斥反应，且创伤较小，且具有供体特异性。此外，检测免疫球蛋白抗体对排斥反应的后期也有帮助。

In this study, we tried to demonstrate the possibility to diagnose acute rejection with detecting anti-donor antibodies using flow cytometry in rat lung transplantation.Donor specific alloantibodies circulating in the peripheral blood already increased significantly 2 days after transplant on the time of mild rejection, whereas there was no evident deposition of alloantibodies in the grafts until day 6.4 and 6 days after transplant, the elevation of the titer of IgM antibodies in the blood was more evident than that of IgG antibodies at this point. On day 8, IgG antibodies continued elevating. On the other hand, IgM antibodies decreased significantly after post-operative day 6.In conclusion, anti-donor antibodies circulating in the peripheral blood could be detected with FCM at the time of mild allograft rejection (A2), and interestingly, before evident deposition of those in the allografts. Detection of IgM alloantibodies with FCM might be useful to identify acute rejection on the early stage with less invasive and donor-specific manner.We also tried to demonstrate the possibility to diagnose acute rejection with detecting anti-donor antibodies in the peripheral blood in cyclosporine treated rat lung transplantation model.Pathological findings of allografts on day 4 were classified in A2, on day 8 and 12 in A2 or A3, and on day 16 in A3 or A4. Donor specific IgM antibodies elevated on day 4, and started decreasing on day 8. On the other hand, the levels of IgG antibody elevated on day 8, and kept gradual increase throughout the observation period.In conclusion, detection of anti-donor IgM antibodies circulating in the peripheral blood with FCM could be useful to identify acute rejection on the early stage with less invasive and donor-specific manner. Additionally, detection of IgG antibodies might be also useful on the later stage of rejection.