The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?
The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?
复制标题
DOI：
10.1111/xen.12771
复制
发表时间：
2022-07
影响因子：
3.9
通讯作者：
Pierson, Richard N., III
中科院分区：
文献类型：
--
作者：
Cooper, David K. C.;Yamamoto, Takayuki;Hara, Hidetaka;Pierson, Richard N., III
关键词：
马里兰州大学团队最近报告了第一位接受基因编辑猪心脏移植的患者的临床过程。虽然猪心脏功能良好>40天，但血清抗猪抗体随后增加，患者在60天后不幸死亡。由于他在移植前的虚弱状态，尽管移植物功能良好，但病人从未茁壮成长过几个星期，他死亡的原因仍然不确定。在观察到抗猪抗体增加的前几天，患者接受了静脉注射人免疫球蛋白（IVIg），并讨论了这是否在其心脏恶化中发挥了作用。此外，mcfDNA检测表明猪巨细胞病毒（CMV）增加，也考虑了其在心功能障碍发展中的可能作用。基于该出版物中提供的有限数据以及我们之前对IVIg是否含有抗TKO猪抗体并因此可能对TKO猪器官异种移植物有害的研究，我们认为抗猪抗体滴度的稳定升高与免疫抑制方案未能阻止诱导的抗TKO猪抗体产生更加一致，而不是来自IVIg的被动输注或移植物中存在猪CMV。虽然马里兰州的经验结果令人失望，但从中吸取了宝贵的教训。我们的注意力被吸引到心脏移植的潜在风险，在一个“去适应”的病人，静脉注射免疫球蛋白，猪巨细胞病毒的传播，并在解释心肌活检结果的困难。
The clinical course of the first patient to receive a gene-edited pig heart transplant was recently reported by the University of Maryland team. Although the pig heart functioned well for >40 days, serum anti-pig antibodies then increased, and the patient sadly died after 60 days. Because of his debilitated pre-transplant state, the patient never thrived despite excellent graft function for several weeks, and the cause of his demise continues to be uncertain. A few days before an increase in anti-pig antibodies was observed, the patient had received intravenous human immunoglobulin (IVIg), and whether this played a role in his cardiac deterioration has been discussed. Furthermore, mcfDNA testing indicated an increase in pig cytomegalovirus (CMV), and its possible role in the development of cardiac dysfunction has also been considered. On the basis of the limited data provided in the publication and on our previous investigations into whether IVIg contains anti-TKO pig antibodies and therefore might be deleterious to TKO pig organ xenografts, we suggest that the steady rise in anti-pig antibody titer was more consistent with the failure of the immunosuppressive regimen to prevent elicited anti-TKO pig antibody production, rather than from the passive transfusion of IVIg or the presence of pig CMV in the graft. Although the outcome of the Maryland experience was disappointing, valuable lessons were learned. Our attention was drawn to the potential risks of heart transplantation in a “deconditioned” patient, the administration of IVIg, the transmission of pig CMV, and of the difficulties in interpreting myocardial biopsy findings.
登录
查看更多内容
影响因子：
7.3
作者：
Goerlich CE;Griffith B;Singh AK;Abdullah M;Singireddy S;Kolesnik I;Lewis B;Sentz F;Tatarov I;Hershfeld A;Zhang T;Strauss E;Odonkor P;Williams B;Tabatabai A;Bhutta A;Ayares D;Kaczorowski DJ;Mohiuddin MM
通讯作者：
Mohiuddin MM
影响因子：
3.9
作者：
Foote, Jeremy B.;Jagdale, Abhijit;Yamamoto, Takayuki;Hara, Hidetaka;Bikhet, Mohamed H.;Schuurman, Henk-Jan;Nguyen, Huy Q.;Ezzelarab, Mohamed;Ayares, David;Anderson, Douglas J.;Fatima, Huma;Eckhoff, Devin E.;Cooper, David K. C.;Iwase, Hayato
通讯作者：
Iwase, Hayato
影响因子：
6.2
作者：
Jordan, SC;Quartel, AW;Tyan, DB
通讯作者：
Tyan, DB
影响因子：
6.6
作者：
Harper, Mary-Ellen;Seifert, Erin L.
通讯作者：
Seifert, Erin L.
影响因子：
8.8
作者：
Baechler, K.;Amico, P.;Schaub, S.
通讯作者：
Schaub, S.