LVAD Implant as a Bridge to Heart Transplantation Is Associated with Allosensitization as Measured by Single Antigen Bead Assay

Shankar, Nisha; Daly, Richard C.; Geske, Jennifer R.; Kushwaha, Sudhir; Timmons, M.J.; Joyce, Lyle D.; Stulak, John; Gandhi, Manish J.; Kremers, Walter K.; Park, Soon; Pereira, Naveen L.

doi:10.1097/tp.0b013e3182985371

Cited by 41 publications

(24 citation statements)

References 16 publications

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“…There are no pediatric studies regarding survival in sensitized VAD patients compared with sensitized non-VAD patients, and data regarding post-transplant survival in the overall population of sensitized pediatric patients are conflicting. 17,18 Adult studies which specifically investigated VAD-associated antibodies support our findings, with no difference in overall survival seen in VAD versus non-VAD patients with PRA >10, 9,11,12,29 even when increased rejection was found. 28…”

Section: Discussionsupporting

confidence: 83%

“…The pathogenicity of the anti‐HLA antibodies produced in association with VAD support is unclear, however. In the adult population, most studies have found no increased rejection in VAD‐sensitized patients; however, a few studies show an increased risk of rejection in patients with VAD‐associated antibodies . Large studies looking specifically at the effect of anti‐HLA antibodies formed in association with VAD support on post‐HTx outcomes in children are lacking.…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

Magdo

Schumacher

et al. 2017

Pediatric Transplantation

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While VAD use in pediatric patients has previously been associated with anti-HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti-HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post-HTx (N=1288) with pre-HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non-MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti-HLA antibodies than non-MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non-MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15-month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti-HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD-associated antibodies and early rejection is unclear and warrants further investigation.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

Magdo

Schumacher

et al. 2017

Pediatric Transplantation

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“…It is possible that leukodepeleted blood transfusions received by VAD patients at our center contributed to sensitization. However, previous studies suggest that such sensitization is independent of transfusions [2] [5] [34]. …”

Section: Discussionmentioning

confidence: 99%

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

See

Clerkin

Kennel

et al. 2017

The Journal of Heart and Lung Transplantation

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Background Pre-transplant sensitization is a limiting factor in solid organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed the generation of Nabs following VAD implantation in pre-transplant sera and examined their contribution to the cardiac allograft outcome. Methods IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant (OHT) recipients, including 128 VAD and 78 no-VAD patients. Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by ELISA. Results No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared to no-VAD patients. This increase was likely due to presence of VAD, as revealed by lower serum IgG Nabs levels before implantation. Lastly, elevated pre-transplant IgG Nabs level was associated with the development of primary graft dysfunction in this patient series. Conclusions Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support the idea of a broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with the development of primary graft dysfunction suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication.

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“…Use of different tests by different laboratories can produce substantially different PRA level resulting in labelling one patient as allosensitized by one laboratory and the same patient as not allosensitized at another laboratory. 35 …”

Section: Discussionmentioning

confidence: 99%

Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation

Chiu

Schaffer

Oyer

et al. 2016

The Journal of Heart and Lung Transplantation

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Introduction Allosensitization has been shown to negatively impact post-heart transplant (HTx) survival even with a negative crossmatch. Whether MCS-related allosensitization is associated with worse post-HTx survival remains controversial. Materials and Methods Adult HTx recipients listed in the United Network for Organ Sharing database (7/06–12/12) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare allosensitized and non-sensitized patients. Kaplan-Meier survival analysis compared matched and unmatched patients in both the MCS and medically managed cohorts. Results We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS devices was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients, HR: 1.07 (0.89–1.28), P=0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality, HR: 1.19 (1.03–1.39), P=0.02. Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when comparing MCS patients who were allosensitized and non-sensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in both unmatched and matched analysis. Conclusions MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

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LVAD Implant as a Bridge to Heart Transplantation Is Associated with Allosensitization as Measured by Single Antigen Bead Assay

Cited by 41 publications

References 16 publications

Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation

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