Antibody-Mediated Rejection

Arias, Manuel; Rush, David; Wiebe, Chris; Gibson, Ian W.; Blydt-Hansen, Tom; Nickerson, Peter; Sellarès, Joana; López-Hoyos, Marcos; Segundo, David San; Crespo-Leiro, María G.; Marzoa-Rivas, Raquel; Barge‐Caballero, Eduardo; Paniagua‐Martin, María J.; Román, Antonio; Serón, Daniel; Böhmig, Georg A.; Schwaiger, Elisabeth

doi:10.1097/tp.0000000000000218

Cited by 13 publications

(2 citation statements)

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“…It has become increasingly evident that memory alloreactive B cells play critical roles in the development of anti-donor HLA antibody responses upon transplantation of allografts in sensitized patients, and that such patients with circulating antibodies have much poorer outcomes compared to patients who do not develop antibodies, including those that had biopsy-confirmed acute rejection 1–5 . Thus there is a need to understand the kinetics of memory B cell formation so that interventions that prevent memory B cell generation and their subsequent reactivation can be rationally designed.…”

Section: Discussionmentioning

confidence: 99%

“…Improved diagnosis of donor-specific antibodies (DSA) has led to the current understanding that antibody-mediated rejection (ABMR) is the leading cause of kidney allograft failure in the clinic 1–5 . Antibody-mediated rejection manifests as microcirculation lesions and specific transcript changes that signify antibody-mediated endothelial injury, interferon-γ effects and the recruitment of natural killer cells.…”

Section: Introductionmentioning

confidence: 99%

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Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation

et al. 2016

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Background The dual role of B cells as drivers and suppressors of the immune responses have underscored the need to trace the fate of B cells recognizing donor MHC Class I and Class II following allograft transplantation. Methods In this study we used donor Class II tetramers to trace the fate of I-Ed-specific B cells following primary immunization with BALB/c spleen cells, or cardiac transplantation, in naïve or sensitized C57BL/6 recipients. We combined this approach with genetic lineage tracing of memory B cells in activation-induced cytidine deaminase regulated Cre transgenic mice (AID-Cre) crossed to the ROSA26-EYFP reporter mice to track endogenous I-Ed-specific memory B cell generation. Results Immunization with BALB/c splenocytes or heart transplantation induced an expansion and differentiation of I-Ed-specific B cells into germinal center B cells, whereas BALB/c heart transplantation into sensitized recipients induced the preferential differentiation into antibody-secreting cells. A 10.8-fold increase in the frequency of I-Ed-specific memory B cells was observed by day 42 postimmunization. Treatment with CTLA4-Ig starting on day 0 or day 7 postimmunization abrogated I-Ed-specific memory B cell generation and sensitized humoral responses, but not if treatment commenced on day 14. Conclusion The majority of donor-specific memory B cells are generated between days 7–14 postimmunization, thus revealing a flexible timeframe whereby delayed CTLA4-Ig administration can inhibit sensitization and the generation of memory graft-reactive B cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation

et al. 2016

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HLA epitope matching in pediatric renal transplantation

2016

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Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications. We review the theory behind human leukocyte antigen (HLA) B cell epitopes and the various systems that have been proposed to define them, including eplets. There is a growing body of clinical evidence suggesting that epitope-based tissue matching may be superior to traditional HLA antigen matching at predicting a range of clinical outcomes. However, additional studies are required to better understand the biological relevance of these systems of defining epitopes and their role in pediatric transplantation.

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