Date: Sunday, May 3, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Room 118-AB
Introduction: Auto-immune responses to cardiac myosin, a heart specific protein has been proposed to be a target auto-antigen resulting in cardiac allograft vasculopathy following transplantation. The goal of the present study is to investigate the kinetics in which passively administered antibodies (Abs) to cardiac myosin induce rejection following syngenic murine heart transplantation and to determine whether anti-myosin mediated immune spreading to other cardiac associated self-antigens (self-Ags) are required to induce rejection.
Methods: C57BL6 hearts (isograft) were transplanted into syngenic C57BL6 mice. Rabbit polyclonal anti-myosin (200¯o;g/ml) was administred intraperitoneally into mice following transplantation (group A) or on days 7,14,21 and 28 after transplantation (group B). Heart palpitation was monitored daily and sera were collected following cessation of heart beats. Abs for self-Ag Myosin, Vimentin were performed using ELISA. Frequency of Ag specific T-cells and the secreting cytokines was determined by ELISpot. Histopathology of the hearts were performed and morphometric analysis of cells infiltrating was determined using Heamtoxylin and Eosin (H&E) staining and immunofluorescence assay.
Results: C57BL6 transplant recipient mice administered with anti-myosin on 0 day rejected the syngenic hearts by day 7. In contrast C57BL6 transplant recipient mice administered with anti-myosin on day 7,14,21 or 28 continued to have functioning cardiac graft till day 30 following transplantation. ELISA results on group A mice serum samples showed significant increase in Ab concentration not only to cardiac myosin but also to vimentin in comparison to animals in group B (p=0.03). Elispot analysis with spleenocytes in group A also showed increased CD4+ T-cells secreting IFN-γ and IL-17 with reduction in IL-10.
Conclusion: We conclude that passive administration of anti-myosin only immediately following syngenic cardiac transplantation results in spreading of immune response to other heart self-Ag vimentin that leads to the isograft rejection most likely due to exposure of cardiac myosin due to ischemia reperfusion injury of the graft. Furthermore, anti-myosin administration results in Ag specific increases in the frequency of IFN-γ and IL-17 cells with marked reduction in IL-10 resulting in loss of peripheral tolerance to self-Ags leading to rejection of syngenic cardiac grafts.
To cite this abstract in AMA style:Sharma M, Gunasekaran M, Benshoff N, Liu W, Gelman A, Mohanakumar T. Passive Administration of Antibodies to Cardiac Myosin Immediately Following Syngenic Cardiac Transplantation Result in Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/passive-administration-of-antibodies-to-cardiac-myosin-immediately-following-syngenic-cardiac-transplantation-result-in-rejection/. Accessed December 7, 2021.
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