Donor specific antibodies association with survival and adverse events after heart transplantation: A single center retrospective study between 2006 and 2021

Akhtar, Waqas; Peterzan, Mark; Banya, Winston; Olwell, Brian; Aghouee, Farveh Vakilian; Brookes, Paul; Dunning, John; Dar, O.

doi:10.1111/ctr.14914

Cited by 4 publications

(7 citation statements)

References 29 publications

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“…Development of DSA is frequently observed after HTx as approximately 25%–30% of patients develop de‐novo DSA within five years from HTx. The majority of these de‐novo DSAs are directed against HLA class II followed by a mixture against HLA class I and II 17–19 . In accordance with these data, we detected de‐novo DSA in 25% of our patients, mainly directed against HLA class II.…”

Section: Discussionsupporting

confidence: 90%

“…De novo DSAs are known to be associated with AMR, 3,20 CAV, 21–25 and mortality 19,24–27 . In keeping, DSA positive patients in our study had more advanced CAV, poorer graft function and higher levels of NT‐proBNP and troponin T. In our study, DSA positive patients with CAV at baseline showed a tendency towards more rapid progression of CAV.…”

Section: Discussionsupporting

confidence: 83%

“…The majority of these de-novo DSAs are directed against HLA class II followed by a mixture against HLA class I and II. [17][18][19] In accordance with these data, we detected de-novo DSA in 25% of our patients, mainly directed against HLA class II. However, the DSA presence is not diagnostic for AMR and the true AMR incidence is unknown.…”

Section: Frequency Of Dsa and Amrsupporting

confidence: 90%

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Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Clemmensen,

Hjort Baatrup,

Bjerre

et al. 2024

Clinical Transplantation

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BackgroundWe aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality.MethodsThe study population comprises 193 consecutive long‐term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow‐up or right censuring on the 30th of June 2023.ResultsDSAs were detected in 50 patients using a cut‐off at MFI ≥1000 and 45 patients using a cut‐off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0–14.4]. DSA positive patients had poorer graft function and higher values of NT‐proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow‐up of five years [4.7–5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6–2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5–4.8)ConclusionsRoutine screening reveals DSA in approximately 25% of long‐term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 83%

Section: Frequency Of Dsa and Amrsupporting

confidence: 90%

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Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Clemmensen,

Hjort Baatrup,

Bjerre

et al. 2024

Clinical Transplantation

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“…53 Furthermore, we found that patients who were both class 1 and 2 DSA positive were at a significantly increased risk for being in the C4d+/DSA+ rather than C4d-/DSA+ group. This observation contributes to existing literature 8,17,20,54,55 and is important for HTx patients that become DSA positive as we did not find the majority of these patients (i.e., C4d-/DSA+ group) to be at increased risk for all cause death, cardiac death or retransplant, CAV, and cardiac allograft dysfunction compared to C4d-/DSA-patients. Further study of class 1 and 2 DSAs, including at a higher molecular resolution 22,56 , may provide additional insights of the risks specific DSAs pose to HTx patients.…”

Section: Discussionsupporting

confidence: 72%

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era

Cusi,

Cardenas,

Tada

et al. 2023

Preprint

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BackgroundC4d immunostaining of surveillance endomyocardial biopsies (EMB) and testing for donor specific antibodies (DSA) are routinely performed in the first year of heart transplantation (HTx) in adult patients. C4d and DSA positivity have not been evaluated together with respect to clinical outcomes in the contemporary era (2010–current).MethodsThis was a single center, retrospective study of consecutive EMBs performed between November 2010 and April 2023. The primary objective was to determine whether history of C4d and/or DSA positivity could predict death, cardiac death, or retransplant. Secondary analyses included cardiac allograft dysfunction and cardiac allograft vasculopathy. Cox proportional hazards models were used for single predictor and multipredictor analyses.ResultsA total of 6,033 EMBs from 519 HTx patients were reviewed for the study. There was no significant difference (p = 0.110) in all-cause mortality or cardiac retransplant between four groups: C4d+/DSA+, C4d+/DSA-, C4d-/DSA+, and C4d-/DSA-. The risk for cardiac mortality or retransplant was significantly higher in C4d+/DSA+ versus C4d-/DSA-patients (HR = 4.73; pc= 0.042) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc= 1.000). Similarly, the risk for cardiac allograft dysfunction was significantly higher in C4d+/DSA+ versus C4d-/DSA- patients (HR 3.26; pc= 0.001) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc= 1.000). Accounting for nonadherence, C4d/DSA status continued to predict cardiac allograft dysfunction but no longer predicted cardiac death or retransplant.ConclusionsMedically adherent C4d+/DSA+ HTx patients show significantly greater risk for cardiac allograft dysfunction but not cardiac mortality or retransplant. In contrast, C4d+/DSA- patients represent a new immunopathologic group with a clinical course similar to that of HTx patients without antibody mediated rejection.

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“…However, it is dnD-SAs that are considered a major threat to transplant recipients [6,7]. In patients with heart transplant (HT), they have been associated with antibody-mediated rejection (AMR) [6,8], cardiac allograft vasculopathy (CAV) [9,10], graft dysfunction [11], and mortality [12][13][14]. They represent one of the main concerns of the HT scientific community because of their tight relationship with long-term outcomes, which have remained barely unchanged over recent years [15].…”

Section: Introductionmentioning

confidence: 99%

De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians

Marco,

López-Azor García,

González Martín

et al. 2023

JCM

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Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients.

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Donor specific antibodies association with survival and adverse events after heart transplantation: A single center retrospective study between 2006 and 2021

Cited by 4 publications

References 29 publications

Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era

De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians

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