Alloantibody induced platelet responses in transplants: Potent mediators in small packages

Kuo, Hsiao Hsuan; Morrell, Craig N.; Baldwin, William M.

doi:10.1016/j.humimm.2012.06.011

Cited by 18 publications

(11 citation statements)

References 70 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[21][22][23] Furthermore, MHC ligation of endothelial cells with and without the help of integrin-β4 can lead to a vasculopathy through complementindependent mechanisms that include: (a) signaling cascades, such as FAK, SCR, PI3k, AKT, mTORC1 [(Raptor) GbL (mTOR)], S6k and S6RP, which cause endothelial/smooth muscle cells to proliferate and release inflammatory mediators; (b) exocytosis of granules containing von Willebrand factor (vWF) and P-selectin, which cause platelet activation and inflammation; (c) up-regulation of fibroblastlike growth factor receptor (FGFR)/FGF biology and its downstream MEK and ERK pathways leading to endothelial/ smooth muscle cell proliferation; and (d) up-regulation of endothelial cell expression of chemokines, which recruit NK cells that express IFN-γ-inducing cells to express more MHC Class I and II, generating further alloimmunity. 3,[21][22][23][24][25][26][27][28][29][30][31] Alternatively, the Fc portion of antibodies can interact with leukocytes via Fc-receptors (FcR) initiating antibodydependent cellular cytotoxicity (ADCC), opsonization and cytokine/chemokine expression, all of which exaggerate allograft damage. 3,[21][22][23][24][25][26][27][28][29] Last, autoantibodies (e.g., vimentin, collagen V, perlecan, Kα1-tubulin, AT1R and MICA) can also cause significant allograft damage as well as amplify alloantibody damage.…”

Section: Mechanisms Of Amrmentioning

confidence: 99%

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation

Levine

Glanville

Aboyoun

et al. 2016

The Journal of Heart and Lung Transplantation

350

351

View full text Add to dashboard Cite

Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications.

show abstract

Section: Mechanisms Of Amrmentioning

confidence: 99%

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation

Levine

Glanville

Aboyoun

et al. 2016

The Journal of Heart and Lung Transplantation

350

351

View full text Add to dashboard Cite

show abstract

“…The interaction of AVA with neutrophils and platelets, produces a pro-thrombotic phenotype which may contribute to the pathogenesis of thrombotic events that occur in autoimmune diseases as well as the thrombotic events that are associated with allograft vasculopathy. Similarly it has been argued that HLA antibodies to MHC class I antigens (constitutively present on platelets) act to potentiate graft rejection via activation of platelets [33]. Two experimental models of cardiac allograft vasculopathy were used to demonstrate that pre-immunisation of recipients with vimentin in CFA results in accelerated occlusion of blood vessels with smooth muscle cells [34].…”

Section: Interaction With Platelets and Graft Vasculopathymentioning

confidence: 99%

Role of anti-vimentin antibodies in allograft rejection

Rose

2013

Human Immunology

View full text Add to dashboard Cite

Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.

show abstract

“…The potential for platelets to participate in AMR has been recognized [18][19][20] but not tested in a relevant model of organ transplantation. Platelets are not easily observed with routine stains because of their small size and lack of nucleus.…”

mentioning

confidence: 99%

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Kuo

Fan²,

Dvorina³

et al. 2015

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100-to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.

show abstract

Alloantibody induced platelet responses in transplants: Potent mediators in small packages

Cited by 18 publications

References 70 publications

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation

Role of anti-vimentin antibodies in allograft rejection

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Contact Info

Product

Resources

About