The Role of Natural Killer Cells in Humoral Rejection

Resch, Thomas; Fabritius, C.; Ebner, Susanne; Ritschl, Paul Viktor; Kotsch, Katja

doi:10.1097/tp.0000000000000757

Cited by 40 publications

(27 citation statements)

References 91 publications

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“…In addition to the CDC pathway, the NK cell-mediated ADCC is another risk factor for chronic cardiac graft rejection213637. NK cell cytotoxic function occurs through natural cytotoxicity or ADCC38.…”

Section: Discussionmentioning

confidence: 99%

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Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Hocine¹,

Costa²,

Dam³

et al. 2017

Sci Rep

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Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.

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Section: Discussionmentioning

confidence: 99%

“…They bind and activate the complement through the Fc region, which results in complement-dependent cytotoxicity (CDC) and incites the acute antibody-mediated rejection1920. HLA antibodies also activate antibody-dependent cell-mediated cytotoxicity (ADCC) through their Fc region engaging receptors on innate immune cells such as natural killer (NK) cells21.…”

mentioning

confidence: 99%

Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Hocine¹,

Costa²,

Dam³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Antibody dependent cell mediated cytotoxicity (ADCC) occurs when the Fc portion of a DSA bound to the transplant endothelium interacts with the Fc receptor on a leucocyte, usually a natural killer cell. This results in the formation of an intercellular synapse that allows the natural killer cell to induce apoptosis of the associated graft endothelium and stimulate the secretion of cytokines which recruit other inflammatory cells to the site . Microvascular inflammation which occurs in the presence of DSA, but in the absence of C4d positivity, may be driven by this manifestation of DSA .…”

Section: Manifestations Of Dsa In the Allograftmentioning

confidence: 99%

Donor specific HLA antibodies & allograft injury: mechanisms, methods of detection, manifestations and management

McCaughan

Tinckam

2018

Transpl Int

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The impact of donor specific HLA antibodies (DSA) on solid organ transplant outcomes has been recognised for over half a century. This article reviews the mechanisms of DSA formation, details the laboratory methods for detecting DSA, discusses the clinical and histological manifestations of DSA in the allograft and explores the options for management of DSA. The challenges posed by pre-existing and de novo DSA are explored with current therapeutic strategies described. A method for stratifying the risk associated with pre-existing DSA is explained and the importance of understanding immunological risk associated with transplantation to facilitate optimal personalised decision making for transplant recipients is highlighted. Future directions for further managing the risk associated with DSA are proposed.

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“…Direct evidence for the role of NK cells in microcirculation injury during ABMR comes from the findings of NK cells and NK cell transcripts in kidney biopsies from patients with donor-specific HLA antibodies (23, 24). Mechanistic studies confirming the role of DSA-dependent NK cell-mediated cytotoxicity in organ allograft rejections is lacking (25). However, clinical trials with cancer therapeutic antibodies have shown that the induction of NK cell-mediated ADCC have direct bearing on organ allograft rejection.…”

Section: Mechanisms Involved In Antibody-mediated Rejection Of Organ mentioning

confidence: 99%

The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection

Rajalingam

2016

Front. Immunol.

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Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR–HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

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The Role of Natural Killer Cells in Humoral Rejection

Cited by 40 publications

References 91 publications

Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Donor specific HLA antibodies & allograft injury: mechanisms, methods of detection, manifestations and management

The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection

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