Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation.
The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.
Tector
A J
AJ
University of Miami, Department of Surgery, Liver and GI Transplant Program, 1801 NW 9th Ave., 5th Floor, Miami, FL 33136, USA. jtector@med.miami.edu
Berho
M
M
Fridell
J A
JA
DiCarlo
A
A
Liu
S
S
Soderland
C
C
Barkun
J S
JS
Metrakos
P
P
Tchervenkov
J I
JI
D000818:Animals; D000910:Antibodies, Heterophile / Q000032:analysis; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000502:physiology; D006084:Graft Rejection; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D017093:Liver Failure / Q000097:blood / Q000601:surgery*; D016031:Liver Transplantation; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010477:Perfusion; D013552:Swine; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D015938:Complement Membrane Attack Complex; D010446:Peptide Fragments; D003179:Complement C3b; D005340:Fibrinogen; D003165:Complement System Proteins; D051561:Complement C3 Convertase, Alternative Pathway