Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: Comparison with standard cryopreserved allografts

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: Comparison with standard cryopreserved allografts
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DOI:
10.1016/s0022-5223(03)00116-8
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发表时间:
2003-07-01
影响因子:
6
通讯作者:
Shaddy, RE
Shaddy, RE
中科院分区:
医学1区
文献类型:
--
作者:
Hawkins, JA;Hillman, ND;Shaddy, RE

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背景:对标准冷冻保存同种异体移植物免疫原性的认识导致了新的脱细胞同种异体移植物的开发(CryoValve SG;CryoLife, Inc, Kennesaw, Ga)。这项初步研究检查了对这些脱细胞同种异体移植物的 HLA 抗体反应,并将其与对标准同种异体移植材料的反应进行比较。方法:我们前瞻性地测量了 14 名接受脱细胞、冷冻保存的儿童(年龄 8.5 +/- 7.9 岁)中出现组反应性 HLA I 类(HLA-A、HLA-B 和 HLA-C)和 II 类(HLA-DR/DQ)同种抗体的频率。同种异体移植,其中 6 个正在进行同种异体移植补片插入,8 个带有带瓣膜的同种异体肺移植物。我们将他们与 20 名接受标准冷冻同种异体移植物植入的历史对照受试者(年龄 1.7 +/- 2.4 岁)进行了比较,其中 8 名带有瓣膜,12 名带有同种异体移植补片。所有患者在术前以及术后 1、3 和 12 个月时均测量了面板反应性抗体水平。采用灵敏的流式细胞术技术测定 HLA I 类和 II 类抗体水平。结果:我们发现,在 1、3 和 12 个月时,脱细胞同种异体移植物中 I 类和 II 类抗体的 I 类和 II 类抗体水平较术前水平略有升高 (P > .05)。与标准同种异体移植物相比,脱细胞同种异体移植物的 I 类和 II 类抗体的组反应性抗体水平显着降低。在功能上,同种异体移植物与脱细胞带瓣移植物相似,显示术后 8 +/- 2.6 个月时回声确定的峰值收缩压梯度为 13 +/- 15 mm Hg,而标准同种异体移植物术后 12 +/- 6 个月测量的梯度为 24±18 mm Hg (P = .11)。 结论:脱细胞移植物引起 I 类和与标准冷冻保存的同种异体移植物相比,在植入后 1、3 和 12 个月时 II 类 HLA 抗体形成。脱细胞移植物的早期血流动力学功能与标准冷冻保存的同种异体移植瓣膜相似。需要进一步的经验来确定脱细胞同种异体移植物的免疫原性降低是否真正允许组织向内生长并改善患者的长期耐久性。
Background: Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material.Methods: We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 +/- 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 +/- 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique.Results: We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P > .05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 +/- 15 mm Hg at 8 +/- 2.6 months postoperatively as compared to a gradient of 24 18 mm Hg measured 12 +/- 6 months postoperatively in standard allografts (P = .11).Conclusions: Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.