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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: SANO Yoshifumi Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (60322228)
• Co-Investigator(Kenkyū-buntansha): DATE Hiroshi Okayama University, Hospital, Lecturer, 医学部・附属病院, 講師 (60252962) ; AOE Motoi Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (80260660) ; NAGAHIRO Itaru Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (00311803) ; SHIMIZU Nobuyoshi Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (90108150) ; ANDOU Akio Okayama University, Graduate School of Medicine and Dentistry, Assistance Professor, 大学院・医歯学総合研究科, 助教授 (70222776)
• Project Period (FY): 2000 – 2001
• Keywords: lung transplantation / acute rejection / anti-donor antibodies / flow cytometry / immunofluoressence / cyclosporine

Research Abstract

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.