Failure to deplete anti-Gal alpha 1-3Gal antibodies after pig-to-baboon organ xenotransplantation by immunoaffinity columns containing multiple Gal alpha 1-3Gal oligosaccharides
Background:The impact of anti-Gal alpha 1-3Gal ( alpha Gal) antibodies on the acute humoral xenograft rejection (AHXR) of pig organs transplanted in baboons is unclear. Methods:Twenty-three baboons underwent heterotopic pig heart transplantation (Tx). Groups A (n = 5) and B (n = 6) received non-tran...
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Veröffentlicht in: | Xenotransplantation (Københaven) 2004-09, Vol.11 (5), p.408-415 |
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Zusammenfassung: | Background:The impact of anti-Gal alpha 1-3Gal ( alpha Gal) antibodies on the acute humoral xenograft rejection (AHXR) of pig organs transplanted in baboons is unclear. Methods:Twenty-three baboons underwent heterotopic pig heart transplantation (Tx). Groups A (n = 5) and B (n = 6) received non-transgenic and human decay accelerating factor (hDAF) pig hearts, respectively, without any treatment. Groups C (n = 5) and D (n = 7) were transplanted with non-transgenic and hDAF organs, respectively, and the exclusive treatment was repeated extracorporeal immunoadsorptions (EIA) before and after Tx with an alpha Gal column containing disaccharide (DI), trisaccharide (TRI) 2 and pentasaccharide (PENTA) oligosaccharides. Results:In group A, 3 of 5 xenografts underwent hyperacute rejection (HAR). No xenograft from groups B, C and D experienced HAR, most of them failing from AHXR. Immediately after Tx and up to day 2, the level of immunoglobulin (Ig)M and IgG anti- alpha Gal DI, TRI2 and TRI6, and anti-pig hemolytic antibody (APHA) antibodies decreased in all the groups by 80 to 96% compared with the concentration present before Tx. From day 3 to AHXR, a sustained increase of anti- alpha Gal IgM DI, TRI2 and TRI6, and APHA occurred in all groups. EIA depleted anti- alpha Gal IgM and APHA before Tx, but it did not modify the increase of these antibodies after Tx. Baboon serum samples before Tx, pre-incubated in vitro with 1 mg/ml of DI, TRI2 and TRI6, had an average of 93% reduction of anti- alpha Gal IgM antibodies specific against each one of these alpha Gal oligosaccharides. In contrast, at AHXR, the average reduction after in vitro pre-incubation with either 1 or 5 mg/ml of DI, TRI2 and TRI6 was 40%. Conclusions:The EIA reduces anti- alpha Gal and APHA antibodies, preventing the HAR of non-transgenic pig hearts transplanted in baboons, as does hDAF expression. However, EIA does not modify the level of anti- alpha Gal IgM and APHA antibodies after Tx nor the AHXR of either non-transgenic or hDAF pig organs. The increase in anti- alpha Gal IgM after Tx was similar for the different antibodies of the anti- alpha Gal polymorphism, and was only partially neutralized in vitro with the specific alpha Gal oligosaccharide. |
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ISSN: | 0908-665X 1399-3089 |
DOI: | 10.1111/j.1399-3089.2004.00152.x |