Hyperacute Rejection. Histopathology of xenograft rejection. The figure shows a comparison between anti-Gal and non-Gal antibody-mediated cardiac xenograft rejection. All panels show hematoxylin and eosin staining. A. Anti-Gal antibody-induced hyperacute rejection of a Gal-positive heart showing widespread intravascular hemorrhage characteristic of HAR. B. Anti-Gal antibody-mediated delayed xenograft rejection (DXR) of a Gal-positive heart on post-operative day 10. The rejected graft shows vascular injury, hemorrhage, and coagulative necrosis characteristic of anti-Gal-mediated DXR. C. Non-Gal antibody-mediated hyperacute rejection of a GTKO heart 90 min after reperfusion showing intravascular hemorrhage similar to that seen in Gal-mediated HAR (panel A). D. Non-Gal-mediated DXR on post-operative day 92 of a Gal-positive CD46 transgenic heart showing thrombotic microangiopathy. The recipient in panel D received chronic alpha-Gal polymer infusions to block anti-Gal antibody. Original magnification A and C 400×, B and D 200× (Panel C adapted from: McGregor CGA, et al. Cardiac xenotransplantation: progress toward the clinic. Transplantation. 2004: 78: 1569–1575.) Not Altered. CC.
Histopathologic insights into the mechanism of anti-non-Gal antibody-mediated pig cardiac xenograft rejection.
Byrne GW, Azimzadeh AM, Ezzelarab M, Tazelaar HD, Ekser B, Pierson RN, Robson SC, Cooper DK, McGregor CG
The hyperacute rejection can occur in minutes of the transplant due to the presence of donor-specific antibodies. This is a very rare phenomenon and usually occurs in a patient with a history of transplantation. The CD4 T-cells react with HLA-class II molecules expressed by the cells of the transplant which initiates the immune response in the recipient and causes rejection of the organ within a few minutes of the transplant.