Desensitization and Heart Transplantation of a Patient With High Levels of Donor-Reactive Anti-Human Leukocyte Antigen Antibodies

Bućin, D; Gustafsson, Ronny; Ekmehag, Björn; Kornhall, Björn; Algotsson, Lars; Lund, Ulla; Otto, Gisela; Koul, Bansi

doi:10.1097/tp.0b013e3181fa93c6

Cited by 14 publications

(5 citation statements)

References 26 publications

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“…Posttransplant treatment consisted of tacrolimus, mycophenolate mofetil, prednisolone, IA, and daclizumab. 72 The use of IA, in combination with pretransplant immunosuppressive drug treatment, temporarily reduced antibody levels, although controlled clinical trials are required to determine appropriate doses of these medications, exposure times, protocols, and effect on rejection. 72 …”

Section: Classic Approaches On Sensitized Patientsmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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Sensitized candidates for heart transplant usually end up on a long waiting list and have an increased risk of rejection, graft loss, and incidence of cardiac allograft vasculopathy. An increasing number of studies have demonstrated the negative effect of preformed and posttransplant antibodies on graft survival. Thus, in sensitized patients, the combination of new, appropriate, desensitization protocols, and monitoring of posttransplant development of donor-specific antibodies may improve short-term and long-term outcomes. Introduction of more-sensitive and more-specific techniques for antibody detection provides a valid tool for assessing the degree of pretransplant HLA histocompatibility, and, therefore, predicting the results of crossmatch in sensitized patients, which are difficult to transplant. Currently, there are no accurate and standard methods to determine the functional characteristics of antibodies detected by solid-phase assay and, therefore, to predict their clinical relevance. Therefore, the future of heart transplantation requires a better understanding of tissue typing techniques and the effect of anti-HLA antibodies on clinical outcome to prevent discrimination against sensitized patients at the time of organ allocation.

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Section: Classic Approaches On Sensitized Patientsmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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“…However, PLEX alone has been shown to exhibit rebound HLA back to pretreatment level after 1 week and IVIg has shown a similarly strong rebound 4 weeks following desensitization. 16,17 In summary, our retrospective study demonstrates that a PIbased AMR treatment strategy among heart transplant recipients reduces DSA, facilitates graft function recovery, and is not associated with significant adverse effects. However, antibody rebound is common, often necessitating multiple cycles of treatment.…”

Section: Discussionmentioning

confidence: 73%

“…Additionally, as PI therapy was utilized in combination with concomitant AMR treatments, it is difficult to directly determine the treatment effect of PI therapy as opposed to other components of the regimens utilized, including PLEX, IVIG, rituximab, and tocilizumab. However, PLEX alone has been shown to exhibit rebound HLA back to pretreatment level after 1 week and IVIg has shown a similarly strong rebound 4 weeks following desensitization 16,17 …”

Section: Discussionmentioning

confidence: 99%

Reduction of HLA donor specific antibodies in heart transplant patients treated with proteasome inhibitors for antibody mediated rejection

Horn,

Xu,

Dibridge

et al. 2023

Clinical Transplantation

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In this project, we describe proteasome inhibitor (PI) treatment of antibody‐mediated rejection (AMR) in heart transplantation (HTX). From January 2018 to September 2021, 10 patients were treated with PI for AMR: carfilzomib (CFZ) n = 8; bortezomib (BTZ) n = 2. Patients received 1–3 cycles of PI. All patients had ≥1 strong donor‐specific antibody (DSA) (mean fluorescence intensity [MFI] > 8000) in undiluted serum. Most DSAs (20/21) had HLA class II specificity. The MFI of strong DSAs had a median reduction of 56% (IQR = 13%–89%) in undiluted serum and 92% (IQR = 53%–95%) at 1:16 dilution. Seventeen DSAs in seven patients were reduced > 50% at 1:16 dilution after treatment. Four DSAs from three patients did not respond. DSA with MFI > 8000 at 1:16 dilution was less responsive to treatment. 60% (6/10) patients presented with graft dysfunction; 4/6 recovered ejection fraction > 40% after treatment. Pathologic AMR was resolved in 5/7 (71.4%) of patients within 1 year after treatment. 9/10 (90%) patients survived to 1 year after AMR diagnosis. Using PI in AMR resulted in significant DSA reduction with some resolution of graft dysfunction. Larger studies are needed to evaluate PI for AMR.

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“… 23 Desensitization using immunoadsorption has been undertaken in combination with intravenous immunoglobulin in the pre-transplant period, and has shown anti-HLA antibody reductions of 50–70%, but with evidence of rebound to pre-treatment levels within 1 week of therapy. 24 Moreover, weekly treatment is required, placing a burden not only on the potential recipient but also on the health teams treating them. Furthermore, because of the requirement for patients to support their own circulation during this treatment, and the anticoagulation required, hypocalcaemia and instability are potential risks, and immunoadsorption is therefore undertaken slowly to minimize these risks.…”

Section: Discussionmentioning

confidence: 99%

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation

et al. 2023

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Background Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. Methods Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). Results A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. Conclusions Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies.

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Desensitization and Heart Transplantation of a Patient With High Levels of Donor-Reactive Anti-Human Leukocyte Antigen Antibodies

Cited by 14 publications

References 26 publications

Current Concepts in Histocompatibility During Heart Transplant

Current Concepts in Histocompatibility During Heart Transplant

Reduction of HLA donor specific antibodies in heart transplant patients treated with proteasome inhibitors for antibody mediated rejection

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation

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