The effects of donor‐specific antibody characteristics on cardiac allograft vasculopathy

Wang, Maggie Haitian; Patel, N.; Zhang, Xiaohai; Kransdorf, E.; Azarbal, Babak; Kittleson, M.; Czer, L.; Kobashigawa, J.A.; Patel, Jignesh

doi:10.1111/ctr.14483

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…23 We also observed a relatively high rate of early CAV, which is associated with DSA. 24 The rate of post-transplant complications in our study including AMR, DSA, and CAV highlights the need for intensive post-transplant surveillance and suggests a role for heightened immunosuppression in desensitized patients.…”

Section: Discussionmentioning

confidence: 60%

Efficacy of bortezomib desensitization among heart transplant candidates

Brinkley

Mangione

Fossey³

et al. 2023

Clinical Transplantation

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Allosensitization is prevalent in heart transplant candidates and is associated with prolonged waiting times and poor outcomes following transplantation. We analyzed the efficacy of a desensitization regimen consisting of plasma exchange, intravenous immunoglobulin, and bortezomib among 25 consecutive sensitized waitlisted candidates at our center from 2016 to 2021. Following desensitization therapies, all C1q negative antibodies were removed from a candidate's unacceptable antigen list. There was a significant decrease in the median number of human leukocyte antigen (HLA) class I (21–15, p = .001) but not class II antibodies (7–6.5, p = .07). There was a significant corresponding decrease in median calculated panel reactive antibodies for class I (90%–74%, p = .004) but not class II (74.5%–75.5%, p = .30). Following desensitization, 76% of patients were transplanted at a median of 91 days. One‐year survival following transplant was 89% with a 33% rate of antibody‐mediated rejection (AMR). In conclusion, a bortezomib desensitization protocol was modestly effective for class I antibodies and allowed successful transplant in most cases when combined with selective crossing of C1q negative antigens.

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Section: Discussionmentioning

confidence: 60%

Efficacy of bortezomib desensitization among heart transplant candidates

Brinkley

Mangione

Fossey³

et al. 2023

Clinical Transplantation

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“…Posttransplant DSA detection has been associated with increased AMR, CAV, and mortality rate, either because of preformed DSA or development of de novo DSA. [67][68][69][70] It is estimated that 25% to 35% of HT recipients develop de novo DSA, primarily class II, with those specific to the DQ locus being most deleterious. 64,71,72 These can emerge both early and late after transplantation, with their persistence (rather than the timing at which they develop) the greatest predictive factor of adverse outcomes.…”

Section: Posttransplant Dsamentioning

confidence: 99%

“…Multiple studies have demonstrated an association between DSA, specifically class II, and development of CAV. 69,89 There is less evidence, however, regarding other molecular biomarkers' association with CAV. A single-center study from Madrid, Spain, evaluated dd-cfDNA of 94 recipients at time of angiography and showed no association between dd-cfDNA and presence of CAV.…”

Section: Biomarkers Of Primary Graft Dysfunction and Cardiac Allograf...mentioning

confidence: 99%

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

Goldberg,

Truby,

Agbor-Enoh

et al. 2023

Circulation

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The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.

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“…C1q binding DSA were also associated with a risk of graft lost [20]. More recently, an association between C1q and CAV was found in adults [37]. In the last international consensus conference on management of antibodies in heart transplantation, only 35% of 103 participants from 75 centers routinely evaluated DSA complement fixing ability in DSA-positive patients [6].…”

Section: Impact Of De Novo Dsa On Risk Of Cav and Mortalitymentioning

confidence: 99%

De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival

Baudry

Pozzi

Aubry

et al. 2022

JCM

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Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patients without preformed DSA on coronary angiography between 2010 and 2012. Angiographies were classified according to CAV ISHLT grading. The primary outcome was a composite criterion of severe CAV or mortality. As the impact of de novo antibodies should be assessed only after appearance, we used a Cox regression with time-dependent covariables. Results: Of the 282 patients, 51(18%) developed de novo DSA during follow-up, 29 patients had DSA with C3d-binding ability (DSA+C3d+), and 22 were without C3d-binding ability (DSA+C3d-). Compared with patients without DSA, DSA+C3d+ patients had an increased risk for the primary outcome of severe CAV or mortality (adjusted HR = 4.31 (2.40–7.74) p < 0.001) and long-term mortality (adjusted HR = 3.48 (1.97–6.15) p < 0.001) whereas DSA+C3d- did not (adjusted HR = 1.04 (0.43–2.47) p = 0.937 for primary outcome and HR = 1.08 (0.45–2.61) p = 0.866 for mortality). Conclusion: According to this large monocentric study in heart transplant patients, donor specific antibodies were associated with worse clinical outcome when binding complement. DSA and their complement-binding ability should thus be screened for to optimize heart transplant patient follow-up.

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The effects of donor‐specific antibody characteristics on cardiac allograft vasculopathy

Cited by 7 publications

References 25 publications

Efficacy of bortezomib desensitization among heart transplant candidates

Efficacy of bortezomib desensitization among heart transplant candidates

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival

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