414.11: Cross-Reacting Antibodies in Xenotransplantation

Habibabady, Zahra; Kinoshita, Kohei; Hara, Hidetaka; Pierson, Richard N.; Cooper, David K.C.

doi:10.1097/01.tp.0000887740.51624.dc

Cited by 3 publications

(7 citation statements)

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“…While AMR can be reversed in allografts, there is no reported successful AMR reversal in pig xenografts as reported a recent comprehensive review. 27 Strategies to prevent or reverse AMR in xenotransplantation are less established, and therapies include antibody depletion, complement inhibition, B cell and plasma cell targeting, and antiinflammatory agents. Combining systemic complement inhibition with anti-inflammatory agents may be the most effective approach, and further genetic engineering of source pigs may be necessary for a comprehensive solution.…”

Section: Immunosuppressionmentioning

confidence: 99%

“…Combining systemic complement inhibition with anti-inflammatory agents may be the most effective approach, and further genetic engineering of source pigs may be necessary for a comprehensive solution. 27 cell-mediated degranulation. 30 Recent investigations also revealed the presence of antibodies against class I SLAs in organ transplant candidates, exhibiting variability-some recognizing a single SLA allele, while others targeted multiple class I SLA proteins.…”

Section: Immunosuppressionmentioning

confidence: 99%

“…As previously noted, antibody‐mediated rejection (AMR) is currently the main immunological barrier to long‐term xenograft success. While AMR can be reversed in allografts, there is no reported successful AMR reversal in pig xenografts as reported a recent comprehensive review 27 . Strategies to prevent or reverse AMR in xenotransplantation are less established, and therapies include antibody depletion, complement inhibition, B cell and plasma cell targeting, and anti‐inflammatory agents.…”

Section: Modifications To the Xenograftmentioning

confidence: 99%

“…Strategies to prevent or reverse AMR in xenotransplantation are less established, and therapies include antibody depletion, complement inhibition, B cell and plasma cell targeting, and anti‐inflammatory agents. Combining systemic complement inhibition with anti‐inflammatory agents may be the most effective approach, and further genetic engineering of source pigs may be necessary for a comprehensive solution 27 . Efforts to characterize human anti‐pig xenoimmune responses lead to the development of an animal model utilizing pig artery tissues transplanted into mice with human immune system 28 …”

Section: Modifications To the Xenograftmentioning

confidence: 99%

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Xenotransplantation literature update March 2023–November 2023

Kamberi,

Meier

2024

Xenotransplantation

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Section: Immunosuppressionmentioning

confidence: 99%

Section: Immunosuppressionmentioning

confidence: 99%

Section: Modifications To the Xenograftmentioning

confidence: 99%

Section: Modifications To the Xenograftmentioning

confidence: 99%

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Xenotransplantation literature update March 2023–November 2023

Kamberi,

Meier

2024

Xenotransplantation

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“…Currently, there is no standard immunosuppressive regimen applied in preclinical pig-to-primate xenotransplantation studies. However, based on the best results achieved in recent NHP studies, a regimen based on an induction with antithymocyte globulin, rituximab, and C1 esterase inhibitor, and a maintenance therapy with an anti-CD154 monoclonal antibody (mAb), rapamycin, methylprednisolone and tocilizumab has been proposed as a possible regimen to prevent the onset of antibody-mediated rejection in preclinical studies [14 ▪ ].…”

Section: Immunological Challengesmentioning

confidence: 99%

Current challenges in xenotransplantation

Vadori,

Cozzi

2024

Current Opinion in Organ Transplantation

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Purpose of review In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation. Recent findings Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies. In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects. Summary Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.

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Novel factors potentially initiating acute antibody‐mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen

Kinoshita,

Maenaka,

Rosales

et al. 2024

Xenotransplantation

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Antibody‐mediated rejection (AMR) is a common cause of graft failure after pig‐to‐nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti‐CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti‐CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute‐onset AMR. The association of a urinary infection with graft rejection has been well‐documented in ABO‐incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.

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414.11: Cross-Reacting Antibodies in Xenotransplantation

Cited by 3 publications

References 0 publications

Xenotransplantation literature update March 2023–November 2023

Xenotransplantation literature update March 2023–November 2023

Current challenges in xenotransplantation

Novel factors potentially initiating acute antibody‐mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen

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