Antibody and complement mediated injury in transplants following sensitization by allogeneic blood transfusion.
BACKGROUND
Many patients on the waiting list for transplants are sensitized from previous blood transfusions, pregnancy, or transplants. We investigated the role of complement in acute and chronic pathology in hearts transplanted to sensitized rats.


METHODS
Blood was transfused from allogeneic PVG.R8 rats or control isogeneic PVG.1U rats to C6-sufficient and -deficient PVG.1U rats. Three weeks later hearts were transplanted from PVG.R8 donors and low-dose cyclosporin A was initiated.


RESULTS
Allogeneic but not isogeneic blood transfusion elicited strong immunoglobulin (Ig) M, IgG1 and IgG2b alloantibody responses. Sensitization caused accelerated acute rejection of cardiac allografts by C6-sufficient recipients (4 days). In contrast, allografts functioned over 40 days in all C6-deficient recipients, but sensitization caused increased interstitial fibrosis and chronic vasculopathy. Circulating alloantibodies were associated with deposits of C4d on the vascular endothelium together with pericapillary accumulation of neutrophils and macrophages in the grafts. In contrast, T cells accumulated in periarterial lymphatics that did not have C4d deposits.


CONCLUSIONS
Presensitization by allogeneic blood transfusion causes accelerated acute graft rejection in the presence of the complete complement cascade. In the absence of C6, macrophages colocalized with deposits of C4d and T cells accumulated in the periarterial lymphatics.
Qian
Zhiping
Z
Transplantation Laboratory, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Lee
Chih-Yuan
CY
Murata
Kazunori
K
Liu
Jinhuan
J
Fox-Talbot
Karen
K
Wasowska
Barbara A
BA
Baldwin
William M
WM
D000818:Animals; D000917:Antibody Formation; D003183:Complement C6 / Q000172:deficiency* / Q000502:physiology*; D017353:Gene Deletion; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007075:Immunoglobulin M / Q000097:blood; D007518:Isoantibodies / Q000097:blood*; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D023421:Models, Animal; D051381:Rats; D011919:Rats, Inbred Strains; D065227:Transfusion Reaction; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D003183:Complement C6; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies