Angiotensin II Type 1 Receptor Antibody Mediated Rejection Following Orthotopic Heart Transplant: A Single Center Experience

Moreno, Jonathan D.; Verma, Amanda; Kopecky, Benjamin; Dehner, Carina; Kostelecky, Nicolas; Schilling, Joel D.; Lavine, Kory J.; Cai, Lin; Vader, Justin

doi:10.1016/j.healun.2020.01.1176

Cited by 2 publications

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“…Next, an extension of anti-AT1R mediated injury to nonkidney organs and a more generalized role for this autoantigen in allo-transplantation is also identifiable (87,88). However, aside from autoimmunity, in our work, we identified that increased genome-wide mismatch was proportional to AT1Rlocus mismatches.…”

Section: At1rsupporting

confidence: 49%

Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms

et al. 2022

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Despite significant improvement in the rates of acute allograft rejection, proportionate improvements in kidney allograft longevity have not been realized, and are a source of intense research efforts. Emerging translational data and natural history studies suggest a role for anti-donor immune mechanisms in a majority of cases of allograft loss without patient death, even when overt evidence of acute rejection is not identified. At the level of the donor and recipient genome, differences in highly polymorphic HLA genes are routinely evaluated between donor and recipient pairs as part of organ allocation process, and utilized for patient-tailored induction and maintenance immunosuppression. However, a growing body of data have characterized specific variants in donor and recipient genes, outside of HLA loci, that induce phenotypic changes in donor organs or the recipient immune system, impacting transplant outcomes. Newer mechanisms for “mismatches” in these non-HLA loci have also been proposed during donor–recipient genome interactions with transplantation. Here, we review important recent data evaluating the role of non-HLA genetic loci and genome-wide donor-recipient mismatches in kidney allograft outcomes.

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Section: At1rsupporting

confidence: 49%

Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms

et al. 2022

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“…The success of using an ARB in conjunction with plasmapheresis/IVIG ± rituximab in anti-AT1R+ heart transplant recipients with allograft dysfunction is not clear. In a recent report, although symptoms were ameliorated, only a fraction of patients experiencing improvement in graft function ( 94 ). Further work is needed to establish how anti-AT1R and other non-HLA antibodies should be managed, particularly in highly HLA sensitized heart transplant candidates.…”

Section: Sensitization and Unique Considerations For The Heart Transplant Candidatementioning

confidence: 99%

Current Desensitization Strategies in Heart Transplantation

Habal

2021

Front. Immunol.

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Heart transplant candidates sensitized to HLA antigens wait longer for transplant, are at increased risk of dying while waiting, and may not be listed at all. The increasing prevalence of HLA sensitization and limitations of current desensitization strategies underscore the urgent need for a more effective approach. In addition to pregnancy, prior transplant, and transfusions, patients with end-stage heart failure are burdened with unique factors placing them at risk for HLA sensitization. These include homograft material used for congenital heart disease repair and left ventricular assist devices (LVADs). Moreover, these risks are often stacked, forming a seemingly insurmountable barrier in some cases. While desensitization protocols are typically implemented uniformly, irrespective of the mode of sensitization, the heterogeneity in success and post-transplant outcomes argues for a more tailored approach. Achieving this will require progress in our understanding of the immunobiology underlying the innate and adaptive immune response to these varied allosensitizing exposures. Further attention to B cell activation, memory, and plasma cell differentiation is required to establish methods that durably abrogate the anti-HLA antibody response before and after transplant. The contribution of non-HLA antibodies to the net state of sensitization and the potential implications for graft longevity also remain to be comprehensively defined. The aim of this review is to first bring forth select issues unique to the sensitized heart transplant candidate. The current literature on desensitization in heart transplantation will then be summarized providing context within the immune response. Building on this, newer approaches with therapeutic potential will be discussed emphasizing the importance of not only addressing the short-term pathogenic consequences of circulating HLA antibodies, but also the need to modulate alloimmune memory.

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Angiotensin II Type 1 Receptor Antibody Mediated Rejection Following Orthotopic Heart Transplant: A Single Center Experience

Cited by 2 publications

References 0 publications

Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms

Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms

Current Desensitization Strategies in Heart Transplantation

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