Does human leukocyte antigens sensitization matter for xenotransplantation?
Does human leukocyte antigens sensitization matter for xenotransplantation?
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DOI：
10.1111/xen.12411
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发表时间：
2018-05
影响因子：
3.9
通讯作者：
Byrne GW
中科院分区：
文献类型：
--
作者：
Byrne GW
主要组织相容性复合物I类和II类人类白细胞抗原（HLA）在获得性免疫中起核心作用，但也是同种异体移植排斥中靶向的主要多态性蛋白。具有高水平的群体反应性抗HLA抗体（PRA）的致敏患者处于早期同种异体移植物损伤、排斥反应、同种异体移植物存活率降低的风险中，并且在移植前通常经历延长的等待时间。使用基因修饰的猪器官的异种移植，为这些高度致敏的患者提供了一个独特的供体器官来源，如果抗HLA抗体，这将同种异体移植物置于危险之中，也不会增强负责异种移植排斥反应的抗猪抗体反应性。最近由于免疫抑制的改善、额外异种聚糖的鉴定和供体猪遗传修饰的持续改善，异种移植疗效有所改善。基因工程猪细胞，缺乏已知的异种聚糖，最大限度地减少90%的人血清样品中的人抗体反应性。对于等待名单中的患者，患者PRA和抗猪抗体反应性的早期比较没有发现相关性，表明PRA水平高的患者异种移植排斥反应的风险没有增加。随后的研究发现，一些，但不是所有的，高度致敏的患者表达抗HLA I类抗体，与猪白细胞抗原（SLA）I类蛋白交叉反应。最近详细的抗原特异性分析表明，来自致敏患者的猪特异性抗SLA抗体结合HLA抗原的有限子集中存在的交叉反应基团。这表明，使用现代遗传学方法，通过供体基因工程或严格的供体选择消除特定SLA等位基因的程序可能使受体抗体反应性最小化，即使是高度致敏的个体。
The major histocompatibility complex class I and class II human leukocyte antigens (HLA) play a central role in adaptive immunity but are also the dominant polymorphic proteins targeted in allograft rejection. Sensitized patients with high levels of panel reactive anti-HLA antibody (PRA) are at risk of early allograft injury, rejection, reduced allograft survival and often experience prolonged waiting times prior to transplantation. Xenotransplantation, using genetically modified porcine organs, offers a unique source of donor organs for these highly sensitized patients if the anti-HLA antibody, which places the allograft at risk, does not also enhance anti-pig antibody reactivity responsible for xenograft rejection. Recent improvements in xenotransplantation efficacy have occurred due to improved immune suppression, identification of additional xenogeneic glycans and continued improvements in donor pig genetic modification. Genetically engineered pig cells, devoid of the known xenogeneic glycans, minimize human antibody reactivity in 90% of human serum samples. For waitlisted patients, early comparisons of patient PRA and anti-pig antibody reactivity found no correlation suggesting that patients with high PRA levels were not at increased risk of xenograft rejection. Subsequent studies have found that some, but not all, highly sensitized patients express anti-HLA class I antibody which crossreacts with swine leukocyte antigen (SLA) class I proteins. Recent detailed antigen specific analysis suggests that porcine specific anti-SLA antibody from sensitized patients binds crossreactive groups present in a limited subset of HLA antigens. This suggests that using modern genetic methods, a program to eliminate specific SLA alleles through donor genetic engineering or stringent donor selection is possible to minimize recipient antibody reactivity even for highly sensitized individuals.
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DOI：
10.1111/j.1600-6143.2011.03846.x
发表时间：
2012-03
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Mohiuddin MM;Corcoran PC;Singh AK;Azimzadeh A;Hoyt RF Jr;Thomas ML;Eckhaus MA;Seavey C;Ayares D;Pierson RN 3rd;Horvath KA
通讯作者：
Horvath KA
影响因子：
158.5
作者：
PATEL, R;TERASAKI, PI
通讯作者：
TERASAKI, PI
影响因子：
3.9
作者：
Hara, Hidetaka;Ezzelarab, Mohamed;Cooper, David K. C.
通讯作者：
Cooper, David K. C.
影响因子：
3.9
作者：
Padler-Karavani V;Varki A
通讯作者：
Varki A
影响因子：
3.9
作者：
Bartholomew, A;Latinne, D;Cosimi, A
通讯作者：
Cosimi, A