Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts.

Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts.
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DOI:
10.4049/jimmunol.1301195
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发表时间:
2013-09-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Soulillou JP
Soulillou JP
中科院分区:
其他
文献类型:
--
作者:
Scobie L;Padler-Karavani V;Le Bas-Bernardet S;Crossan C;Blaha J;Matouskova M;Hector RD;Cozzi E;Vanhove B;Charreau B;Blancho G;Bourdais L;Tallacchini M;Ribes JM;Yu H;Chen X;Kracikova J;Broz L;Hejnar J;Vesely P;Takeuchi Y;Varki A;Soulillou JP

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异种来源的无细胞材料在世界范围内用作异种移植物,目前正在进行活猪胰岛的 I 期试验。然而,关于异种移植后猪内源性逆转录病毒(PERV)的传播以及受体对异种抗原的长期免疫反应的信息有限。我们分析了接受活猪皮敷料长达 8 周的烧伤患者的血液中是否存在 PERV,以及他们针对猪抗原的长期(最长 34 年)免疫反应的水平和性质。虽然没有发现 PERV 基因组物质或抗 PERV 抗体反应的证据,但我们观察到这些患者中抗 αGal 抗体适度增加,以及高且持续的抗非 αGal IgG 反应。针对非人唾液酸Neu5Gc的抗体构成了抗非αGal反应,其在唾液酸罐阵列上的识别模式与没有猪皮治疗的烧伤患者的识别模式不同。这些数据表明,抗 Neu5Gc 抗体可能是猪异种移植物长期接受的障碍。由于抗 Neu5Gc 抗体可以促进慢性炎症,因此活体猪组织和无细胞猪组织植入物在受体体内的长期安全性值得进一步评估。
Acellular materials of xenogenic origin are used worldwide as xenografts and Phase I trials of viable pig pancreatic islets are currently being performed. However, limited information is available on transmission of porcine endogenous retrovirus (PERV) after xenotransplantation and on the long-term immune response of recipients to xenoantigens. We analyzed the blood of burn patients who had received living pig skin dressings for up to 8 weeks for the presence of PERV as well as for the level and nature of their long term (maximum 34 years) immune response against pig antigens. Whilst no evidence of PERV genomic material or anti PERV antibody response was found, we observed a moderate increase in anti αGal antibodies and a high and sustained anti non-αGal IgG response in those patients. Antibodies against the non-human sialic acid Neu5Gc constituted the anti non-αGal response with the recognition pattern on a sialogly can array differing from that of burn patients treated without pig skin. These data suggest that anti-Neu5Gc antibodies may represent a barrier for long-term acceptance of porcine xenografts. As anti-Neu5Gc antibodies can promote chronic inflammation, the long-term safety of living and acellular pig tissue implants in recipients warrants further evaluation.
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