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. 1990;3(1):39-49.
doi: 10.3109/08941939009140335.

Immunodepletion in xenotransplantation

R Shapiro  1 , A G Tzakis, V Scantlebury, L Makowka, R Watt, A Oks, K Yanaga, L Podesta, A Casavilla, S Wos, et al.
Affiliations

Immunodepletion in xenotransplantation

R Shapiro et al. J Invest Surg. 1990.

Abstract

Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group.

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Figures

Figure 1
Figure 1
Schematic view of staphylococcal protein A binding to the Fc receptor of IgG and IgM.
Figure 2
Figure 2
Schematic view of Sepharose-bound protein A binding to antibody.
Figure 3
Figure 3
CITEM 10 (Excorim, Dupont), a computer-controlled device to remove IgG and IgM.
Figure 4
Figure 4
Immunodepletion, Blood from patient is separated into plasma and red cells; plasma is passed over Staph-A column in CITEM 10; immunodepleted plasma is returned with red cells to patient.
Figure 5
Figure 5
IgG depletion in five dogs given multiple treatments of immunodepletion.
Figure 6
Figure 6
IgM depletion in five dogs given multiple treatments of immunodepletion.
Figure 7
Figure 7
IgO depletion in six dogs given one treatment of immunodepletion.
Figure 8
Figure 8
IgM depletion in six dogs given one treatment of immunodepletion.
See this image and copyright information in PMC

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