Pre- and posttransplantation allosensitization in heart allograft recipients: Major impact of de novo alloantibody production on allograft survival

Ho, Eric K.; Vlad, George; Vasilescu, Elena R.; Torre, Ludwika de la; Colovai, Adriana I.; Burke, Elizabeth; Deng, Mario C.; Schwartz, Joseph; Marboe, Charles C.; Mancini, Donna; Opelz, Gerhard; Suciu‐Foca, Nicole

doi:10.1016/j.humimm.2010.10.013

Cited by 110 publications

(96 citation statements)

References 38 publications

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“…31 In addition, patients were monitored after the transplant for HLA class I and II antibody production, and statistical analyses showed that posttransplant alloantibody development was a risk factor associated not only with the AMR onset but also with a low survival rate. 33 Several recent reports have emphasized the clinical effect not only of preformed, but also especially of de novo anti-HLA alloantibodies on graft outcomes in heart transplant recipients. [33][34][35] In particular, de novo anti-HLA donor-specific antibody development was associated with increased rejection, CAV, and poor survival.…”

Section: Introductionmentioning

confidence: 99%

“…33 Several recent reports have emphasized the clinical effect not only of preformed, but also especially of de novo anti-HLA alloantibodies on graft outcomes in heart transplant recipients. [33][34][35] In particular, de novo anti-HLA donor-specific antibody development was associated with increased rejection, CAV, and poor survival. 30,31,36 Indeed, antibodies against class I or class II antigens seem to have negative effects.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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“…Recently, the role of B cell responses and alloantibodies in transplantation has come to the forefront as more evidence demonstrates that these responses contribute to graft rejection, particularly in the chronic setting (44)(45)(46)(47). Clinically, there have been reports of effectiveness of B cell-depleting agents, complement blocking agents, or proteasome inhibitors, which block plasma cell Ab production, in transplantation (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Transient Low-Dose Methotrexate Induces Tolerance to Murine Anti-Thymocyte Globulin and Together They Promote Long-Term Allograft Survival

Joseph¹,

Neff²,

Richard³

et al. 2012

The Journal of Immunology

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Rabbit anti-thymocyte globulin (Thymoglobulin) effectively treats transplant rejection but induces anti-rabbit Ab responses, which limits routine readministration. Aiming to tolerize anti-rabbit responses, we coadministered a brief methotrexate regimen with a murine version of Thymoglobulin (mATG) for effects on anti-mATG Abs and cardiac allotransplantation in mice. Although both single and three courses of methotrexate could significantly inhibit anti-drug Ab titers to repeated mATG treatment, surprisingly, the single course given at the first mATG administration was most effective (>99% reduction). The transient methotrexate treatment also significantly improved pharmacokinetics and pharmacodynamics of repeated mATG administration. In the cardiac allograft model, the combination of transient mATG and methotrexate given only at the time of transplant dramatically improved allograft survival (>100 d) over either agent alone (<30 d). Anti-drug Ab titers were reduced and mATG exposure was increased which resulted in prolonged rather than enhanced mATG-mediated effects when combined with methotrexate. Moreover, methotrexate administration significantly reduced alloantibodies, suggesting that methotrexate not only decreases anti-drug Ab responses but also reduces Ab responses to multiple tissue-derived alloantigens simultaneously. These data suggest that mATG and methotrexate together can provide long-term allograft survival potentially through the induction of immune tolerance.

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“…Lower titer alloantibody associated with chronic AMR activates endothelial intracellular signaling cascades [3] inducing cell proliferation manifested ultimately as transplant vasculopathy and deterioration of graft function. Ho [4] recently reported results of a large cohort (n=950) of transplants with long term follow-up including biopsies and HLA antibody testing. Development of AMR had significant impact on long term graft survival (16% versus 63% in the AMR negative group at 12 years).…”

Section: Role Of Alloantibody In Acute Rejection and Chronic Allografmentioning

confidence: 99%

Allosensitization and the Ventricular Assist Device: Dual Evolution of Technology

Coppage¹

2013

Recent Advances in the Field of Ventricular Assist Devices

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Pre- and posttransplantation allosensitization in heart allograft recipients: Major impact of de novo alloantibody production on allograft survival

Cited by 110 publications

References 38 publications

Current Concepts in Histocompatibility During Heart Transplant

Current Concepts in Histocompatibility During Heart Transplant

Transient Low-Dose Methotrexate Induces Tolerance to Murine Anti-Thymocyte Globulin and Together They Promote Long-Term Allograft Survival

Allosensitization and the Ventricular Assist Device: Dual Evolution of Technology

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