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Failure to deplete anti‐Galα1‐3Gal antibodies after pig‐to‐baboon organ xenotransplantation by immunoaffinity columns containing multiple Galα1‐3Gal oligosaccharides
Author(s) -
Mañez Rafael,
Domenech Nieves,
Centeno Alberto,
LopezPelaez Eduardo,
Crespo Fabian,
Juffe Alberto,
Duthaler Rudolf O.,
Katopodis Andreas G.
Publication year - 2004
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2004.00152.x
Subject(s) - xenotransplantation , antibody , baboon , transplantation , immunoadsorption , microbiology and biotechnology , chemistry , andrology , immunology , medicine , biology , endocrinology
Background: The impact of anti‐Gal α 1‐3Gal ( α 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 α 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‐ α 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‐ α Gal IgM DI, TRI2 and TRI6, and APHA occurred in all groups. EIA depleted anti‐ α 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‐ α Gal IgM antibodies specific against each one of these α 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‐ α 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‐ α Gal IgM and APHA antibodies after Tx nor the AHXR of either non‐transgenic or hDAF pig organs. The increase in anti‐ α Gal IgM after Tx was similar for the different antibodies of the anti‐ α Gal polymorphism, and was only partially neutralized in vitro with the specific α Gal oligosaccharide.