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Liver allograft rejection in sensitized recipients: Observations in a clinically relevant small animal model

Nakamura, K and Murase, N and Becich, MJ and Furuya, T and Todo, S and Fung, JJ and Starzi, TE and Demetris, AJ (1993) Liver allograft rejection in sensitized recipients: Observations in a clinically relevant small animal model. American Journal of Pathology, 142 (5). 1383 - 1391. ISSN 0002-9440

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Abstract

A sequential analysis of liver allograft rejection in sensitized rats using immunopathological and ultrastructural microscopy is described. Lewis rats were primed with four ACI skin grafts and challenged with an arterialized ACI orthotopic liver allograft 14 to 17 weeks later. The sensitization resulted in a mix of IgG and IgM lymphocytotoxic antibodies at a titer of 1:512 at the time of transplantation. Specificity analysis of pretransplant immune sera revealed a predominance of IgG anti-class I major histocompatibility complex (RTI) antibodies with a minor IgG fraction showing apparent endothelial cell specificity (non-RTI). This level of sensitization was associated with accelerated graft failure in 3 to 5 days from mixed humoral and cellular rejection. Sequential analysis of serial posttransplant graft biopsies revealed diffuse vascular IgG deposition and platelet thrombi in portal veins and periportal sinusoids within 3 minutes after reperfusion. This was followed by endothelial cell hypertrophy and vacuolization, periportal hepatocyte necrosis, arterial spasms, focal large bile duct necrosis, and hilar mast cell infiltration and degranulation. However, the liver allografts did not fail precipitously and hyperacute rejection was not seen. Kupffer cell phagocytosis of the sinusoidal platelets began as early as 30 minutes posttransplant and by 24 hours, the platelet thrombi had decreased. Cholangioles appeared focally at the edge of the limiting plates by 2 to 3 days, apparently in response to earlier periportal hepatocyte damage. A mononuclear portal and perivenular infiltrate became evident at 3 days, and graft failure was attributed to both antibody and cell-mediated rejection (Furuya et al: Preformed lymphocytotoxic antibodies: Hepatology 1992, 16: 1415-1422). The model described resembles observations in crossmatch positive human liver allograft recipients. The mechanisms of hepatic graft resistance to antibody mediated rejection and the possible long term consequences of early damage to the biliary tree are discussed.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nakamura, K
Murase, N
Becich, MJbecich@pitt.eduBECICH
Furuya, T
Todo, S
Fung, JJ
Starzi, TE
Demetris, AJ
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 December 1993
Date Type: Publication
Journal or Publication Title: American Journal of Pathology
Volume: 142
Number: 5
Page Range: 1383 - 1391
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0002-9440
Other ID: uls-drl:31735062113778, Starzl CV No. 1589
Date Deposited: 08 Apr 2010 17:27
Last Modified: 27 Jan 2019 02:55
URI: http://d-scholarship.pitt.edu/id/eprint/4975

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