Preformed Lymphocytotoxic Antibodies: the Effects of Class, Titer and Specificity on Liver Vs. Heart Allografts

Abstract

The effect on liver and heart allograft survival (ACI rats to Lewis rats) was studied after three methods of recipient presensitization and after different intervals between sensitization and transplantation. With comparable lymphocytotoxic antibody titers, liver allografts always survived longer than heart grafts. The titer, class and specificity of the antibodies varied with the method of sensitization. Four skin grafts produced IgG and IgM lymphocytotoxic antibody titers of 1 : 2,000 to 4,000. The IgG fraction was shown to have hepatic vascular endothelial specificity by indirect immunofluorescence. These primed recipients hyperacutely rejected both heart and liver allografts, which showed vascular deposition of IgG antibodies. Survival of either kind of graft was inversely proportional to the Iymphocytotoxic antibody titer and length of time after placement of the last skin graft. Presensitization with a single heterotopic heart graft produced an even higher mixed IgG and IgM lymphocytotoxic antibody titer of 1: 8,000 but with less IgG vascular endothelial specificity. These animals also hyperacutely rejected heart or liver grafts with tissue deposition of IgG but less consistently and with a weaker correlation with lymphocytotoxic antibody titers and time after sensi· tization. Sensitization with two pretransplant blood transfusions produced the lowest titer (1: 500 to 1,000) and the least IgG vascular endothelial specificity. Liver allograft survival was routinely enhanced in these animals, and little effect was seen on heart grafts. Collectively, the experiments showed that the liver is not only resistant to antibody-mediated rejection relative to the heart but is more easily enhanced. A more precise characterization of preformed antibodies may increase the ability to predict the outcome of liver transplantation in sensitized recipients or guide pretransplant strategies to foster enhancing antibodies.

The Biological Basis of and Strategies for Clinical Xenotransplantation

“…The relative resistance of the transplanted liver to antigraft antibodies that cause hyperacute allograft and xenograft rejection (Kamada et al 1981, Starzl et al 1974, Houssin et al 1985, Furuya et al 1992, as well as the ability of the liver to shield other organs from humoral rejection (Fung et al 1988, Flye et al 1990) is of special interest for xenotransplantation (Valdivia et al 1993c). The shielding from humoral rejections is MHC-restricted for allografts (Fung et al 1988, Flye et al 1990).…”

Significance of C4d staining in ABO-identical/compatible liver transplantation

“…In clinical practice, hyperacute rejection is very rare, and some initial reports suggested that liver allografts were much more resistant to humoral rejection than other solid organ allografts. [1][2][3] It is natural for the liver to be considered an 'immunologically privileged organ', and cadaveric donor liver transplantation is usually performed without considering human leukocyte antigen (HLA) matching. 4 However, other studies including the most recent reported that some cases of positive lymphocyte crossmatch or positive panel reactive antibody were associated with decreased liver graft survival.…”

Histopathological Syndromes of Liver Allograft Rejection and Recurrent Disease

“…Difficulties are encountered in establishing the diagnosis because: 1 Liver allografts are large, able to absorb high antibody loads, especially anti-class I HLA [94], and are resistant to AMR-related damage [3,83,87,95,96]; 2 Immune deposits pointing toward an underlying injury cause are: (a) ephemeral [82,87]; (b) can be associated with other insults (see below); and (c) are more easily detected in frozen sections [97]; and 3 Clinicopathologic similarities exist between AMR and preservation injury, sepsis, and biliary or vascular complications [82,87]. Intrahepatic immune deposits are ephemeral in AMR, even when using the more sensitive technique of immunofluorescence on frozen tissue [30,82,87].…”