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

• Published in: Xenotransplantation (Københaven) Vol. 11; no. 5; pp. 408 - 415
• Main Authors: Manez, Rafael, Domenech, Nieves, Centeno, Alberto, Lopez-Pelaez, Eduardo, Crespo, Fabian, Juffe, Alberto, Duthaler, Rudolf O, Katopodis, Andreas G
• Format: Journal Article
• Language: English
• Published: 01.09.2004
• Subjects: Papio
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1111/j.1399-3089.2004.00152.x

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.