A. Pascher et al., APPLICATION OF IMMUNOAPHERESIS FOR DELAYING HYPERACUTE REJECTION DURING ISOLATED XENOGENEIC PIG-LIVER PERFUSION, Transplantation, 63(6), 1997, pp. 867-875
Background. Extracorporeal liver perfusion in hepatic coma, used to el
iminate toxic metabolites causing hepatic encephalopathy, is limited b
y the antibody (Ab) and complement-mediated hyperacute rejection of di
scordant xenografts, Thus, the efficacy of highly selective immunoadso
rption columns to deplete xenoreactive human anti-porcine antibodies b
efore ex vivo liver perfusion was examined in this study. Methods. Eig
hteen domestic pigs were hepatectomized according to standard techniqu
es, The livers were ex vivo perfused for 4 hr, The perfusion protocol
closely followed the physiological conditions of a human liver, Parame
ters of liver function and damage were analyzed, Three groups were for
med differing in the treatment of the perfusate, As basic control, liv
ers were perfused with heparinized human blood (group 1; n=6), Immunoa
pheresis was applied in group 3 (n=6), Immunoapheresis was performed u
sing Ig Therasorb columns consisting of sheep-anti-human IgG Abs coval
ently coupled to Sepharose CL-4B, Additionally, the effect of pure Sep
harose CL-4B without immobilized Ab was tested in group 2 (n=6). Resul
ts. The use of Ig Therasorb 100 columns in group 3 resulted in a reduc
tion of IgG, IgM, and IgA in the order of 95.0%, 72.3%, and 81.5%, res
pectively, In group 2, IgG, IgM, and IgA were lowered by 30% to 39%, D
etermination of liver-specific enzymes and tolerance tests revealed a
significant reduction of cellular damage and functional restrictions i
n group 3 compared with the control groups. Conclusions. Immunoapheres
is conducted according to this protocol appears to be an effective app
roach for delaying antibody-mediated hyperacute xenogeneic rejection.