Current and future challenges in therapy for antibody-mediated rejection

Nair, Nandini; Ball, Timothy R.; Uber, Patricia A.; Mehra, Mandeep R.

doi:10.1016/j.healun.2011.02.002

Cited by 55 publications

(27 citation statements)

References 28 publications

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“…6 Indeed, the choice of immunosuppressive approach in relation to patient preoperative characteristics is the most appropriate tool in reducing the incidence of early and late complications, and to achieve better results in terms of survival and quality of life of the transplanted patient. 62,63 The knowledge of antibody-mediated immune response mechanisms has provided insights for potential therapeutic intervention, but complete elimination of donor-specific anti-HLA antibodies during AMR is rarely achieved with traditional antihumoral therapy. 4 There are several strategies available to reduce sensitization in patients waiting for a heart transplant and to treat AMR.…”

Section: Virtual Crossmatchmentioning

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: Virtual Crossmatchmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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“…Several studies demonstrate that control of memory is a major challenge in transplantation (24)(25)(26)(27)(28)(29)(30)(31)(32)(33). CNI remain the cornerstones to control T mem .…”

Section: Introductionmentioning

confidence: 99%

Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory T Cells

Siepert

Ahrlich

Vogt

et al. 2012

American Journal of Transplantation

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Recent data suggest that donor-specific memory T cells (T mem ) are an independent risk factor for rejection and poor graft function in patients and a major challenge for immunosuppression minimizing strategies. Many tolerance induction protocols successfully proven in small animal models e.g. costimulatory blockade, T cell depletion failed in patients. Consequently, there is a need for more predictive transplant models to evaluate novel promising strategies, such as adoptive transfer of regulatory T cells (Treg).We established a clinically more relevant, lifesupporting rat kidney transplant model using a high responder (DA to LEW) recipients that received donorspecific CD4 + / 8 + GFP + T mem before transplantation to achieve similar pre-transplant frequencies of donorspecific T mem as seen in many patients. T cell depletion alone induced long-term graft survival in naïve recipients but could not prevent acute rejection in T mem + rats, like in patients. Only if T cell depletion was combined with permanent CNI-treatment, the intragraft inflammation, and acute/chronic allograft rejection could be controlled long-term. Remarkably, combining 10 days CNI treatment and adoptive transfer of Tregs (day 3) but not Treg alone also induced longterm graft survival and an intragraft tolerance profile (e.g. high TOAG-1) in T mem + rats. Our model allows evaluation of novel therapies under clinically relevant conditions.

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“…22 Strikingly, treatment paradigms for AMR are still not clearly established and outcomes remain poor, especially for AMR associated with allograft dysfunction. 23 Of the variables identified in the Kilic study, 4 black race and female sex have been associated with an increased propensity for AMR, especially in the setting of a positive donor-specific cross match and elevated circulating donor-directed antibodies. 22 Moreover, heightened antibody expression and subsequent propensity to AMR is uniquely associated with the increasing application of mechanical circulatory devices.…”

Section: Emergence and Recognition Of Antibody-mediated Rejectionmentioning

confidence: 97%