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Comparative Study
. 1992 Dec;16(6):1415-22.
doi: 10.1002/hep.1840160618.

Preformed lymphocytotoxic antibodies: the effects of class, titer and specificity on liver vs. heart allografts

T Furuya  1 , N Murase, K Nakamura, J Woo, S Todo, A J Demetris, T E Starzl
Affiliations
Comparative Study

Preformed lymphocytotoxic antibodies: the effects of class, titer and specificity on liver vs. heart allografts

T Furuya et al. Hepatology. 1992 Dec.

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 lymphocytotoxic 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 sensitization. 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Figures

Fig. 1
Fig. 1
The changes in LAb titer after sensitization (mean ± S.D.). Titers more than 9 wk after heart sensitization and more than 15 wk after skin sensitization were significantly different than initial titers at 2 wk (*p < 0.01). In addition, titers less than 6 wk after heart sensitization and 4 wk after skin sensitization were significantly higher than after blood sensitization (**p < 0.01).
Fig. 2
Fig. 2
Graft survival time after skin sensitization. Heart or liver grafts surviving more than 3 days showed a mixed humoral and cellular rejection (open circles), whereas those failing before 3 days showed more humoral rejection (closed circles). *Median survival time of ACI heart graft (6 days, N = 7). **Median survival time of ACI liver graft (10 days, N = 7) in unsensitized LEW recipients.
Fig. 3
Fig. 3
Correlation between heart or liver graft survival and LAb titer after skin or heart sensitization. Skin/heart = heart graft survival and cytotoxic antibody titer after skin sensitization. Regression equation: log10 (Y) = 3.5713 – 0.41796X, r = 0.6766, p < 0.01. Skin/liver = liver graft survival and cytotoxic antibody titer after skin sensitization. Regression equation: log10 (Y) = 1.9549 – 0.15054X, r = 0.5690, p < 0.01. Heart/heart = heart graft survival and cytotoxic antibody titer after heart sensitization. Regression equation: log10 (Y) = 2.3070 – 0.18928X, r = 0.5042, p < 0.01. Heart/liver = liver graft survival and cytotoxic antibody titer after heart sensitization. Regression equation: log10 (y) = 1.1692 – 0.071396X, r = 0.2811; NS.
Fig. 4
Fig. 4
Graft survival after heart sensitization. *Median survival of ACI heart grafts (6 days, N = 7). **Median survival of ACI liver graft (10 days, N = 7) in unsensitized LEW recipient.
Fig. 5
Fig. 5
Cytotoxic antibody titer before and after heart or liver transplantation. Heart Tx = heart transplantation; liver Tx = liver transplantation; before Tx = titers before heart or liver transplantation; after Tx = titers after heart or liver transplantation; < 4 days = grafts rejected within 4 days; ≥4 days = grafts survived for 4 or more days.
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References

    1. Terasaki PI, Marchioro TL, Starzl TE. Sero-typing of human lymphocyte antigens: preliminary trials on long-term kidney homograft survivors. Conference and workshop on histocompatibility testing; Washington DC: National Academy of Sciences, National Research Council; 1965. pp. 83–96.
    1. Kissmeyer-Neilsen F, Olsen S, Peterson VP, Fjeldborg O. Hyper-acute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet. 1966;2:662–665. - PubMed
    1. Iwatsuki S, Iwaki Y, Kano T, Klintmalm G, Koep LJ, Weil R, Starzl TE. Successful liver transplantation from crossmatch positive donors. Transplant Proc. 1981;13:286–288. - PMC - PubMed
    1. Takaya S, Duquesnoy R, Iwaki Y, Demetris AJ, Yagihasi A, Bronsther O, Iwatsuki S, et al. Positive crossmatch in primary human liver allografts under cyclosporine or FK506 therapy. Transplant Proc. 1991;23:396–399. - PMC - PubMed
    1. Gubernatis G, Lauchart W, Jonker M, Steinhoff G, Bornscheuer A, Neuhaus P, Van Es AA, et al. Signs of hyperacute rejection of liver grafts in rhesus monkeys after donor-specific presensitization. Transplant Proc. 1987;19:1082–1083. - PubMed

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