The role of B cell immunity in VCA graft rejection and acceptance

Kaufman, Christina L.; Cascalho, Marília; Özyürekoğlu, Tuna; Jones, Christopher M.; Ramirez, Allan; Roberts, Tiffany K.; Tien, Huey; Moreno, Rodrigo; Galvis, Elkin J.; Tsai, Tsu‐Min; Palazzo, Michelle D; Farner, Scott; Platt, Jeffrey L.

doi:10.1016/j.humimm.2019.03.002

Cited by 18 publications

(10 citation statements)

References 66 publications

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“…In the classical pathway, along with C4a and C4b, C4d is subsequently cleaved and can covalently bind to the endothelium, serving as a diagnostic tool of AMR in solid organ transplantation ( 38 , 39 ). Yet, AMR remains rarely reported in VCA recipients ( 40 ). In the few cases of AMR in VCA, no clear correlation between C4d deposition and DSA formation was found ( 41 , 42 ).…”

Section: Acute Allograft Rejectionmentioning

confidence: 99%

“…The B cell-based production of DSAs holds a pivotal role in the overlap of B cell biology and VCA and can be subdivided into preexisting versus de-novo DSAs, with the latter typically occurring within 3 months post-transplantation ( 25 , 40 , 125 , 126 ). In theory, the immunogenic components of VCA grafts (especially skin and mucosal tissue) and the frequently encountered presensitization (i.e., the formation of preformed potentially donor-specific antibodies) of VCA recipients through previous blood transfusions and/or surgical procedures may predispose this patient population to AMR.…”

Section: Beyond Antibody Production - B Cells As Secondary Effectorsmentioning

confidence: 99%

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Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Knoedler

Lee

et al. 2023

Front. Immunol.

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Vascularized composite allotransplantation (VCA) is an evolving field of reconstructive surgery that has revolutionized the treatment of patients with devastating injuries, including those with limb losses or facial disfigurement. The transplanted units are typically comprised of different tissue types, including skin, mucosa, blood and lymphatic vasculature, muscle, and bone. It is widely accepted that the antigenicity of some VCA components, such as skin, is particularly potent in eliciting a strong recipient rejection response following transplantation. The fine line between tolerance and rejection of the graft is orchestrated by different cell types, including both donor and recipient-derived lymphocytes, macrophages, and other immune and donor-derived tissue cells (e.g., endothelium). Here, we delineate the role of different cell and tissue types during VCA rejection. Rejection of VCA grafts and the necessity of life-long multidrug immunosuppression remains one of the major challenges in this field. This review sheds light on recent developments in decoding the cellular signature of graft rejection in VCA and how these may, ultimately, influence the clinical management of VCA patients by way of novel therapies that target specific cellular processes.

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Section: Acute Allograft Rejectionmentioning

confidence: 99%

Section: Beyond Antibody Production - B Cells As Secondary Effectorsmentioning

confidence: 99%

Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Knoedler

Lee

et al. 2023

Front. Immunol.

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“…For example, some patients were initially reported to be DSA-positive, but subsequently it was determined that the DSA found were non-specific reactions. 57 The focal vasculopathy detected in one artery by histology did not evolve into clinically significant vasculopathy, and this subject continues to have minimal vasculopathy at more than 18 years posttransplant, although chronic skin changes are apparent. Assignment of a subject who did not present with DSA prior to (non-HLA antibodies were also tested and were negative, and IgG and IgM deposition on the amputated graft was also negative), but only after, amputation may not help to characterize the role of DSA by artificially skewing the small population.…”

Section: Observations Of Cr In Human Vca Recipientsmentioning

confidence: 85%

Defining chronic rejection in vascularized composite allotransplantation—The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation

et al. 2020

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Objectives: This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation. Methods: The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, “Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is.” Results: The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed. Conclusions: It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.

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“…It is thought that chronic rejection is predominantly T-cell mediated, however, recent studies have suggested that B cells may also play a role in the process. 42,43 In the literature, very few cases of antibody mediated rejection have been reported in VCA recipients, possibly due to a multitude of proposed mechanisms in which VCA differs from solid organ transplant. 44 However, although seemingly rare, monitoring of the humoral response through biomarkers as well as the desensitization of transplant recipients prior to operation may minimize these episodes.…”

Section: Chronic Rejectionmentioning

confidence: 99%

Facial Transplantation

2021

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Facial transplantation represents a unique surgical solution for challenging facial injury patterns in which conservative reconstructive techniques fail to provide a satisfactory functional and aesthetic result. With advances in the field of vascularized composite allotransplantation over the past 15 years, more than 40 of these procedures have been performed worldwide with two recent reports of facial re-transplantation. In this article we discuss the multidisciplinary approach that is required for successful transplantation as well as the surgical techniques used and postoperative management. With ongoing research, recent technological innovation, and increased efforts to promote greater generalizability and transparency in this field, patients with these complex injuries will continue to see improvements in their treatment options, and thus quality of life.

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The role of B cell immunity in VCA graft rejection and acceptance

Cited by 18 publications

References 66 publications

Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Facial Transplantation

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