Failure to deplete anti-Galalpha1-3Gal antibodies after pig-to-baboon organ xenotransplantation by immunoaffinity columns containing multiple Galalpha1-3Gal oligosaccharides.
Xenotransplantation
; 11(5): 408-15, 2004 Sep.
Article
em En
| MEDLINE
| ID: mdl-15303977
ABSTRACT
BACKGROUND:
The impact of anti-Galalpha1-3Gal (alphaGal) 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 alphaGal 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-alphaGal 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-alphaGal IgM DI, TRI2 and TRI6, and APHA occurred in all groups. EIA depleted anti-alphaGal 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-alphaGal IgM antibodies specific against each one of these alphaGal 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-alphaGal 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-alphaGal IgM and APHA antibodies after Tx nor the AHXR of either non-transgenic or hDAF pig organs. The increase in anti-alphaGal IgM after Tx was similar for the different antibodies of the anti-alphaGal polymorphism, and was only partially neutralized in vitro with the specific alphaGal oligosaccharide.
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Base de dados:
MEDLINE
Assunto principal:
Transplante Heterólogo
/
Anticorpos Heterófilos
/
Dissacarídeos
/
Rejeição de Enxerto
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article