Studies on the removal of anti-pig xenoantibodies in the human by plasmapheresis/immunoadsorption

Autor: Stefan Magnusson, Eva Hallberg, Staffan Björckv, Michael E. Breimer, Bo E. Samuelsson, Valeri Strokan, Lennart Rydberg
Rok vydání: 1995
Předmět:
Zdroj: Xenotransplantation. 2:253-263
ISSN: 1399-3089
0908-665X
DOI: 10.1111/j.1399-3089.1995.tb00106.x
Popis: Removal of human preformed natural anti-pig antibodies from the blood is a prerequisite before xenografting between pig and man can be performed. This work explores the effect of plasmapheresis and immunoadsorption (protein-A sepharose) on the reduction and recurrence of anti-pig antibodies in 14 patients. The anti-pig antibody changes were evaluated by lymphocy to toxic, hemagglutinating, and endothelial cell ELISA techniques. The changes induced showed a similar pattern with all three techniques used. In addition, plasma from plasmapheresis treatments were perfused through pig kidneys and the reduction of anti-pig antibodies was estimated by the mentioned in vitro techniques. The anti-pig antibody titers could be reduced to low levels, but not completely eliminated, by 3–4 plasmapheresis sessions. The titers gradually returned to pretreatment levels or higher in a period of 1–2 weeks. A few patients showed signs of a more rapid resynthesis reaching pretransplant levels in 3–4 days. Protein A immunoadsorption satisfactory removed IgG but not IgM antibodies. In vitro perfusion of pig kidneys at 37°C showed a rapid reduction of anti-pig antibody titers of 3–4 titer steps. The combination of 3–4 plasma exchanges followed by in vitro pig kidney perfusion completely removed all anti-pig antibodies. Reduction of the anti-pig lymphocyte and erythrocyte antibody titers by soluble oligosaccharides carrying terminal Galoc-epitopes was only partly successful. A 40–60% inhibition was achieved by 5–10 mg saccharide/ml serum and no clear inhibition difference between di- and trisaccharides was found. Inhibition of plasma obtained after 3–4 plasmapheresis treatments with soluble Galα1-di- and trisaccharides resulted in very low anti-pig titers. Therefore one feasible pretreatment procedure, before pig to human xenotransplantation could be plasmapheresis for major reduction of anti-pig antibody titer followed by neutralisation of the remaining antibodies by addition of soluble oligosaccharides or immunoadsorption with Galα-1-columns.
Databáze: OpenAIRE
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