在猪到狒狒的器官异种移植后，使用含有多种α1-3半乳糖寡糖的免疫亲和柱未能清除抗α1-3半乳糖抗体。

Failure to deplete anti-Galalpha1-3Gal antibodies after pig-to-baboon organ xenotransplantation by immunoaffinity columns containing multiple Galalpha1-3Gal oligosaccharides.

作者信息

Mañez Rafael, Domenech Nieves, Centeno Alberto, Lopez-Pelaez Eduardo, Crespo Fabian, Juffe Alberto, Duthaler Rudolf O, Katopodis Andreas G

机构信息

Transplantation Division, Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain.

出版信息

Xenotransplantation. 2004 Sep;11(5):408-15. doi: 10.1111/j.1399-3089.2004.00152.x.

DOI:10.1111/j.1399-3089.2004.00152.x

PMID: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.

摘要

背景

抗α - 半乳糖（αGal）抗体对移植于狒狒体内的猪器官急性体液异种移植排斥反应（AHXR）的影响尚不清楚。

方法

23只狒狒接受了异位猪心脏移植（Tx）。A组（n = 5）和B组（n = 6）分别接受了非转基因猪心脏和人衰变加速因子（hDAF）猪心脏，未进行任何治疗。C组（n = 5）和D组（n = 7）分别移植了非转基因器官和hDAF器官，唯一的治疗方法是在Tx前后用含有二糖（DI）、三糖（TRI）2和五糖（PENTA）寡糖的αGal柱进行重复体外免疫吸附（EIA）。

结果

A组5个异种移植中有3个发生了超急性排斥反应（HAR）。B组、C组和D组均无异种移植发生HAR，大多数因AHXR失败。Tx后即刻至第2天，所有组中免疫球蛋白（Ig）M和IgG抗αGal DI、TRI2和TRI6以及抗猪溶血抗体（APHA）抗体水平与Tx前浓度相比下降了８０％至９６％。从第3天至AHXR，所有组中抗αGal IgM DI、TRI2和TRI6以及APHA持续增加。EIA在Tx前消耗了抗αGal IgM和APHA，但未改变Tx后这些抗体的增加。Tx前的狒狒血清样本在体外与1mg/ml的DI、TRI2和TRI6预孵育后，针对这些αGal寡糖中每一种的抗αGal IgM抗体平均减少93％。相比之下，在AHXR时，与1mg/ml或5mg/ml的DI、TRI2和TRI6体外预孵育后的平均减少率为40％。

结论

EIA可降低抗αGal和APHA抗体，防止移植于狒狒体内的非转基因猪心脏发生HAR，hDAF表达也有此作用。然而，EIA并未改变Tx后抗αGal IgM和APHA抗体水平，也未改变非转基因或hDAF猪器官的AHXR。Tx后抗αGal IgM的增加在抗αGal多态性的不同抗体中相似，并且在体外仅被特异性αGal寡糖部分中和。