Alpha-Gal Specific IgG Immune Response after Implantation of Bioprostheses
Alpha-Gal Specific IgG Immune Response after Implantation of Bioprostheses
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DOI：
10.1055/s-0029-1185395
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发表时间：
2009-06-01
影响因子：
1.5
通讯作者：
Ankersmit, H. J.
中科院分区：
文献类型：
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作者：
Mangold, A.;Szerafin, T.;Ankersmit, H. J.
背景：我们先前已经证明，α-Gal(Gal Alpha 1.3-Gal beta 1-4GlcNAc-R)表位是心脏外科生物假体上存在的相关异种抗原，并能诱导α-Gal特异性的IgM免疫反应。材料和方法：我们分别在心脏手术前、术后10天和术后3个月采集了接受生物瓣膜置入术(n=19)和机械瓣膜置换术(n=8)的患者的血浆样本。用ELISA法测定α-Gal特异性免疫球蛋白及其亚类。3首次手术后1周内(n=1)或12~15个月(n=2)需再次手术患者的生物假体组织标本。结果：植入生物假体后3个月，α-半乳糖特异性免疫球蛋白较术前显著升高(P<0.001)，也显著高于对照组(P<；0.05)。IgG3是针对α-Gal的主要亚类(P<；0.05，手术前和术后值)。激光共聚焦显微镜分析显示，植入后1周植入的生物假体在胶原基质中含有IB4/DAPI阳性细胞。相反，在12个月后再次手术的患者中，猪组织中完全缺乏IB4/DAPI。结论：我们的结果表明，植入生物假体后3个月内，与对照组相比，植入生物假体能诱导针对α-Gal承载细胞的特异性体液免疫反应。植入12个月后完全没有IB4/DAPI阳性结构表明，通过先前暴露在人体血液循环中，携带α-Gal的细胞发生了特定的降解。
Background: We have previously shown that the alpha-Gal (Gal alpha 1.3-Gal beta 1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation.Materials and Methods: We collected plasma samples from patients Who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac Surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI).Results: alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major Subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI.Conclusion: Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive Structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood Circuit.