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

抗供体抗体与肺移植急性排斥反应的关系

• 批准号: 12671311
• 负责人: SANO Yoshifumi
• 金额: $ 0.83万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671311/
• 关键词: lung transplantation; acute rejection; anti-donor antibodies; flow cytometry; immunofluoressence; cyclosporine

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.

本研究应用流式细胞术检测大鼠肺移植中的供者特异性抗体，以探讨其诊断急性排斥反应的可能性，结果发现，供者特异性抗体在移植后第2天即已显著升高，而移植物中的抗体直到移植后第6.4天和第6天才有明显沉积，此时血液中IgM抗体滴度的升高比IgG抗体滴度的升高更明显。第8天，IgG抗体继续升高。IgM抗体在术后第6天明显下降。总之，在轻度排斥反应（A2）时，即在移植物中明显沉积之前，FCM就可以检测到外周血中循环的抗供体抗体。应用流式细胞术检测同种异体IgM抗体，可作为早期诊断急性排斥反应的一种方法，具有创伤小、特异性强等优点，并在环孢素A处理的大鼠肺移植模型上，通过检测外周血中抗供体抗体，探讨了急性排斥反应的诊断价值。在第16天在A3或A4中。供体特异性IgM抗体在第4天升高，并在第8天开始降低。结论：流式细胞术检测外周血中抗供者IgM抗体，可作为早期诊断急性排斥反应的一种方法，具有创伤小、特异性强等优点。此外，IgG抗体的检测也可能是有用的排斥反应的后期阶段。