Portal Venous Donor-specific Transfusion in Conjunction with Sirolimus Prolongs Renal Allograft Survival in Nonhuman Primates

Overview

Journal Am J Transplant

Publisher Elsevier

Specialty General Surgery

Date 2008 Nov 4

PMID 18976300

Citations 2

Authors

K K Dhanireddy

D A Bruno

T A Weaver

H Xu

X Zhang

F V Leopardi

D A Hale

A D Kirk

Affiliations

Soon will be listed here.

Abstract

Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration.

Citing Articles

Heart grafts tolerized through third-party multipotent adult progenitor cells can be retransplanted to secondary hosts with no immunosuppression.

Eggenhofer E, Popp F, Mendicino M, Silber P, Vant Hof W, Renner P Stem Cells Transl Med. 2013; 2(8):595-606.

PMID: 23836805 PMC: 3726139. DOI: 10.5966/sctm.2012-0166.

Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion.

Lo D, Anderson D, Weaver T, Leopardi F, Song M, Farris A Am J Transplant. 2013; 13(2):320-8.

PMID: 23311611 PMC: 3558532. DOI: 10.1111/j.1600-6143.2012.04342.x.

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