Is sensitization to pig antigens detrimental to subsequent allotransplantation?

Li, Qi; Hara, Hidetaka; Zhang, Zhongqiang; Breimer, Michael E.; Wang, Yi; Cooper, D. K. C.

doi:10.1111/xen.12393

Cited by 41 publications

(33 citation statements)

References 37 publications

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“…Historically, reactions to XTx have not only been shaped by reports of scientific progress, inherent biases, religious views, and cultural beliefs. 9,10 The relatively high acceptance rate reported here possibly demonstrates change and optimism regarding the solution offered by XTx. Given the somewhat charged history of XTx, 11 it is not surprising that there was decreased enthusiasm for its use if outcomes were anticipated to be inferior to those of allotransplantation.…”

Section: Commentmentioning

confidence: 76%

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians

Padilla

Sorabella

Carlo

et al. 2020

World J Pediatr Congenit Heart Surg

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Background: Cardiac transplantation in early childhood is limited by scarcity of organ donors. Advances in cardiac xenotransplantation (XTx) research suggest that xenografts may one day represent an alternative to allografts. We sought to determine the attitudes among surgeons and cardiologists in the field of pediatric cardiac transplantation toward the potential use of XTx if this clinical option were to become a reality. Methods: A Likert-scale anonymous survey addressing the use of XTx in pediatric patients was sent to members of the Congenital Heart Surgeons (CHS) Society and the Pediatric Heart Transplant Society. Results were described and compared between the two surgeon/physician groups. Results: Ninety-two CHS and 42 pediatric transplant cardiologists (PTC) responded (N = 134). The potential acceptance of XTx was high in both groups, assuming risks and results were similar to those of cardiac allotransplantation (88% CHS vs 81% PTC; P = .07). When asked if they would recommend a xenograft, if the results were anticipated to be inferior to those of cardiac allotransplantation, as a bridge to a human heart, potential acceptance fell dramatically but remained higher among CHS than PTC (41% vs 17%, p 0.02). Approximately only one-third of CHS and half of PTC preferred primary cardiac XTx for hypoplastic left heart syndrome if there was no waitlist time and had similar outcomes to allotransplantation. Conclusions: Our findings suggest that potential acceptance of XTx by CHS and PTC would not be a major barrier if XTx demonstrated similar outcomes to allotransplantation. Acceptance by other congenital heart stakeholders remains to be investigated.

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Section: Commentmentioning

confidence: 76%

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians

Padilla

Sorabella

Carlo

et al. 2020

World J Pediatr Congenit Heart Surg

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“…There have been numerous surveys of relatively small groups within the community, and also of members of the healthcare professions. 51,52 Several surveys and focus groups have been carried…”

Section: Pub LI C At Titude S To Clini C Al Xenotr Ans Pl Antationmentioning

confidence: 99%

Pig kidney xenotransplantation: Progress toward clinical trials

Cooper

Hara

Iwase

et al. 2020

Clinical Transplantation

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Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.

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“…Heterotopic auxiliary pig liver xenotransplantation could reduce the risks associated with the subsequent definitive liver allotransplantation. Furthermore, as the current evidence is that sensitization to pig xenoantigens is not associated with any increase in anti‐HLA antibodies (ie, does not sensitize the patient to HLA) . a pig xenograft would not be detrimental to obtaining or maintaining a subsequent allograft.…”

Section: Discussionmentioning

confidence: 83%

A review of pig liver xenotransplantation: Current problems and recent progress

Zhang

Yang

et al. 2019

Xenotransplantation

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Pig liver xenotransplantation appears to be more perplexing when compared to heart or kidney xenotransplantation, even though great progress has been achieved. The relevant molecular mechanisms involved in xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia, are complex, and need to be systematically investigated. The deletion of expression of Gal antigens in the liver graft highlights the injurious impact of nonGal antigens, which continue to induce humoral rejection. Innate immunity, particularly mediated by macrophages and natural killer cells, interplays with inflammation and coagulation disorders. Kupffer cells and liver sinusoidal endothelial cells (LSECs) together mediate leukocyte, erythrocyte, and platelet sequestration and phagocytosis, which can be exacerbated by increased cytokine production, cell desialylation, and interspecies incompatibilities. The coagulation cascade is activated by release of tissue factor which can be dependent or independent of the xenoreactive immune response. Depletion of endothelial anticoagulants and anti-platelet capacity amplify coagulation activation, and interspecies incompatibilities of coagulation-regulatory proteins facilitate dysregulation. LSECs involved in platelet phagocytosis and transcytosis, coupled with hepatocyte-mediated degradation, are responsible for thrombocytopenia. Adaptive immunity could also be problematic in long-term liver graft survival. Currently, relevant evidence and study results of various genetic modifications to the pig donor need to be fully determined, with the aim of identifying the ideal transgene combination for pig liver xenotransplantation. We believe that clinical trials of pig liver xenotransplantation should initially be considered as a bridge to allotransplantation. K E Y W O R D Scoagulation dysregulation, genetically engineered, liver, pig, xenotransplantation

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Is sensitization to pig antigens detrimental to subsequent allotransplantation?

Cited by 41 publications

References 37 publications

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians

Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians

Pig kidney xenotransplantation: Progress toward clinical trials

A review of pig liver xenotransplantation: Current problems and recent progress

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