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接受生物瓣心脏瓣膜的患者的免疫反应:去细胞瓣膜缺乏反应。

Immune response in patients receiving a bioprosthetic heart valve: lack of response with decellularized valves.

机构信息

AutoTissue GmbH, Goerzallee 305 D, Berlin, Germany.

出版信息

Tissue Eng Part A. 2011 Oct;17(19-20):2399-405. doi: 10.1089/ten.TEA.2011.0046. Epub 2011 Jun 20.

DOI:10.1089/ten.TEA.2011.0046
PMID:21557643
Abstract

Conventional biological heart valves treated with glutaraldehyde (GA) reveal a limited lifespan due to calcification. This is assumed to be an immune response initiated process, which is not seen with decellularized valves. However, their immunological potential is still a matter of debate. Therefore, serum samples from patients undergoing heart valve surgery were obtained before (Pre), after (Post), and 9-12 months after operation (Follow Up). Immunoglobulin G (IgG) and M (IgM) antibodies against porcine collagen I and α-Gal (Gal-alpha1,3-Gal-beta1,4-GlcNac-R) were determined for decellularized and GA treated valves. Antibody titers for collagen type I revealed no significant alteration for both types of valves. However, a considerable anti-α-Gal antibody response was observed in patients with GA-treated porcine valves. In detail, IgM antibodies were increased during follow up (p<0.05), whereas decellularized valves revealed a minor decrease in the IgM response (p<0.001). IgG antibodies were considerably increased with GA-treated porcine (p<0.05) and bovine (p<0.01) xenografts, whereas there was lack of response with decellularized valves. This indicates that GA treatment is not sufficient to eliminate immune response to the α-Gal epitope completely. Future investigations will have to verify whether immune response to α-Gal can be linked to the limited durability of conventional valves.

摘要

用戊二醛(GA)处理的传统生物心脏瓣膜由于钙化而显示出有限的寿命。这被认为是一种免疫反应引发的过程,在去细胞化瓣膜中不会出现这种情况。然而,它们的免疫潜力仍然存在争议。因此,从接受心脏瓣膜手术的患者中获得手术前(Pre)、手术后(Post)和手术后 9-12 个月(Follow Up)的血清样本。针对去细胞化和 GA 处理的瓣膜,测定了针对猪胶原蛋白 I 和 α-Gal(Gal-alpha1,3-Gal-beta1,4-GlcNac-R)的免疫球蛋白 G(IgG)和 M(IgM)抗体。两种类型的瓣膜对胶原蛋白 I 的抗体滴度均未发生明显变化。然而,在接受 GA 处理的猪瓣膜患者中观察到相当大的抗-α-Gal 抗体反应。具体而言,IgM 抗体在随访期间增加(p<0.05),而去细胞化瓣膜的 IgM 反应则略有下降(p<0.001)。GA 处理的猪(p<0.05)和牛(p<0.01)异种移植物的 IgG 抗体明显增加,而去细胞化瓣膜则没有反应。这表明 GA 处理不足以完全消除对 α-Gal 表位的免疫反应。未来的研究将不得不验证对 α-Gal 的免疫反应是否与传统瓣膜的有限耐久性有关。

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