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

在这项研究中，我们试图证明利用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。移植后2天，在轻度排斥反应时，外周血循环供体特异性同种异体抗体已明显升高，而移植后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抗体滴度的升高比IgG抗体滴度的升高更为明显。第8天，IgG抗体继续升高。另一方面，IgM抗体在术后第6天显著下降。综上所述，FCM可以检测到外周血中循环的抗供体抗体在同种异体移植物轻度排斥反应时（A2），有趣的是，在同种异体移植物中明显沉积之前。用流式细胞术检测IgM同种异体抗体可能有助于早期识别急性排斥反应，且具有较少的侵入性和供体特异性。我们也尝试在环孢素处理的大鼠肺移植模型中，通过检测外周血抗供体抗体来诊断急性排斥反应的可能性。同种异体移植物第4天病理表现分为A2级，第8、12天分为A2或A3级，第16天分为A3或A4级。供体特异性IgM抗体在第4天升高，并在第8天开始下降。另一方面，IgG抗体水平在第8天升高，并在整个观察期保持逐渐升高。综上所述，FCM检测外周血中抗供者IgM抗体可用于早期识别急性排斥反应，且具有较小的侵入性和供者特异性。此外，IgG抗体的检测在排异反应的后期也可能有用。

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.