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Jeffrey L. Platt - One of the best experts on this subject based on the ideXlab platform.
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acute Vascular Rejection and accommodation divergent outcomes of the humoral response to organ transplantation
Transplantation, 2004Co-Authors: Josie M Williams, Zoie E Holzknecht, Timothy B Plummer, Gregory J Brunn, Shu S Lin, Jeffrey L. PlattAbstract:Background. The most difficult barrier to organ transplantation is humoral Rejection, a condition initiated by binding of antibodies to blood vessels in the graft. Fortunately, humoral Rejection is not the only outcome of antibody binding to the graft. In some cases, accommodation, a condition in which the graft does not undergo humoral injury despite the existence of humoral immunity directed against it, occurs and the graft remains seemingly inured. The mechanism underlying accommodation is uncertain, but changes in the function of antibodies, changes in the target antigen, and changes in the graft imparting resistance to injury have been implicated. Methods. Using the swine-to-baboon cardiac xenograft model, we asked which mechanism(s) may distinguish acute Vascular Rejection from accommodation. Results. In both acute Vascular Rejection and accommodation, antibodies were bound and complement activated in blood vessels of the graft. However, in acute Vascular Rejection, the full complement cascade was activated; while in accommodation, the complement cascade was interrupted, suggesting complement was inhibited in the latter condition. In acute Vascular Rejection, heparan sulfate and syndecan-4-phosphate, which can aid in complement control, were nearly absent, whereas in accommodation these were present in heightened amounts. Conclusion. These findings suggest that control of complement may underlie accommodation, at least in part, and raise the possibility that this control and possibly other protective mechanisms could be exerted by heparan sulfate.
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apoptosis and cellular activation in the pathogenesis of acute Vascular Rejection
Circulation Research, 2002Co-Authors: Zoie E Holzknecht, Karisha L Kuypers, Timothy B Plummer, Josie Williams, Matilda Bustos, Gregory James Gores, Gregory J Brunn, Jeffrey L. PlattAbstract:Acute Vascular or humoral Rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute Vascular Rejection by tracing the processes during the development of acute Vascular Rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-x L , was not detected until acute Vascular Rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute Vascular Rejection and progressed through the disease process. These findings suggest that acute Vascular Rejection is caused by an active metabolic process and not by apoptosis in the endothelium.
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the role of anti galalpha1 3gal antibodies in acute Vascular Rejection and accommodation of xenografts
Transplantation, 2000Co-Authors: Shu S Lin, Guerard W Byrne, Lisa E Diamond, William Parker, M J Hanaway, Gonzalo V Gonzalezstawinski, Christine L Lau, Duane R Davis, John S Logan, Jeffrey L. PlattAbstract:BACKGROUND A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute Vascular Rejection, which can destroy a Vascularized xenograft over a period of hours to days. Acute Vascular Rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galalpha1-3Gal epitopes in porcine tissue, initiate this phenomenon. METHODS AND RESULTS Specific depletion of anti-Galalpha1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Galalpha1-3Galbeta1-4GlcAc, averted the development of acute Vascular Rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gala1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation. CONCLUSION These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute Vascular Rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.
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expression of tissue factor mrna in cardiac xenografts clues to the pathogenesis of acute Vascular Rejection
Transplantation, 2000Co-Authors: T Nagayasu, Timothy B Plummer, Soheyla Saadi, Robert A Holzknecht, Jeffrey L. PlattAbstract:Background. Acute Vascular Rejection destroys Vascularized xenografts over a period of hours to days and is now considered the major hurdle to the clinical application of xenotransplantation. The hallmark of acute Vascular Rejection is diffuse intraVascular coagulation; however, the pathogenesis of coagulation is a matter of controversy. One line of evidence points to activated endothelial cells and another to activated inflammatory cells as a source of tissue factor and thus as a primary cause of this lesion. The distinction between the two mechanisms inducing coagulation in the xenograft provides an opportunity for specific intervention. Methods. To explore these mechanisms, we studied the expression of tissue factor mRNA by in situ reverse transcriptase-polymerase chain reaction in relation to the histopathologic manifestations of acute Vascular Rejection in guinea pig hearts transplanted into rats treated by cobra venom factor to avoid the hyperacute Rejection. Results. Three hours after transplantation and before the deposition of fibrin, tissue factor mRNA was expressed in the endothelial cells lining small and medium blood vessels and in smooth muscle cells of guinea pig cardiac xenografts. Sixteen hours after transplantation, while rat tissue factor mRNA was expressed only in occasional infiltrating cells, cardiac xenografts showed prominent deposits of fibrin in small vessels. Maximum expression of tissue factor on rat infiltrating cells was observed 48 hr after transplantation. Conclusions. These results suggest that in acute Vascular Rejection, coagulation is initiated on the donor Vascular system, while the procoagulant characteristics of infiltrating cells may reflect a response to tissue injury rather than a cause.
Pierre Gianello - One of the best experts on this subject based on the ideXlab platform.
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characterization of baboon anti porcine igg antibodies during acute Vascular Rejection of porcine kidney xenograft
Xenotransplantation, 2002Co-Authors: Jeanpaul Dehoux, Bernardo De La Parra, Dominique Latinne, Herve Bazin, Pierre GianelloAbstract:In the pig-to-baboon model, the removal of anti-porcine natural antibodies abrogates hyperacute Vascular Rejection (HAVR), but the xenograft then undergoes an acute Vascular Rejection (AVR) concomitantly to the appearance of newly formed anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim of this work was to characterize the anti-porcine antibodies during AVR. Sera from anti-IgM-treated animals were assessed prior to the graft and at the time of AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine antibodies concentration as well as the IgG subtypes. The same sera were tested on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i) the cytolytic complement-dependent activity and (ii) the E-selectin expression. The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to discriminate the presence of Gal epitopes from the recognition of other porcine epitopes. We found that both anti-porcine IgM and IgG antibodies presented a significantly increased cytolytic activity and E-selectin expression on PAECs during AVR. These characteristics are related to an important increase of the antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl IgG1 subclass production, whereas the K affinity remained unchanged. The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies.
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Characterization of baboon anti‐porcine IgG antibodies during acute Vascular Rejection of porcine kidney xenograft
Xenotransplantation, 2002Co-Authors: Jeanpaul Dehoux, Bernardo De La Parra, Dominique Latinne, Herve Bazin, Pierre GianelloAbstract:In the pig-to-baboon model, the removal of anti-porcine natural antibodies abrogates hyperacute Vascular Rejection (HAVR), but the xenograft then undergoes an acute Vascular Rejection (AVR) concomitantly to the appearance of newly formed anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim of this work was to characterize the anti-porcine antibodies during AVR. Sera from anti-IgM-treated animals were assessed prior to the graft and at the time of AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine antibodies concentration as well as the IgG subtypes. The same sera were tested on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i) the cytolytic complement-dependent activity and (ii) the E-selectin expression. The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to discriminate the presence of Gal epitopes from the recognition of other porcine epitopes. We found that both anti-porcine IgM and IgG antibodies presented a significantly increased cytolytic activity and E-selectin expression on PAECs during AVR. These characteristics are related to an important increase of the antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl IgG1 subclass production, whereas the K affinity remained unchanged. The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies.
Kazunari Tanabe - One of the best experts on this subject based on the ideXlab platform.
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Clinicopathologic Analyses of Chronic Vascular Rejection After Kidney Transplantation
Transplantation proceedings, 2020Co-Authors: Tomokazu Shimizu, Hideki Ishida, Kazuya Omoto, Kazunari TanabeAbstract:Abstract Aim We discuss the clinicopathologic analyses of cases of biopsy specimens (BS) after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of chronic Vascular Rejection (CVR). Patients CVR was diagnosed in 30 renal allograft BS obtained from 23 renal transplant patients being followed up at the Department of Urology and Transplant Surgery, Toda Chuo General Hospital, between January 2010 and August 2017. Results CVR was diagnosed at a median of 33.1 months post-transplantation. Among the 23 patients, 14 had a history of Rejection. Among the 30 BS showing evidence of CVR, the CVR was mild (cv1 on Banff’s classification) in 19, moderate (cv2) in 6, and severe (cv3) in 5. We then classified the 30 BS showing evidence of CVR by their overall histopathologic features as follows: cv alone was seen in 9 (30%), cv + antibody-mediated Rejection (AMR) in 11 (37%), and cv + T-cell-mediated Rejection (TCMR) in 8 (27%). Loss of the renal allograft occurred during the observation period in 2 patients (9%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 6 (26%). Conclusions Our study results suggest that AMR contributes to CVR in 30% to 40% of cases, TCMR in 20% to 30% of cases, isolated v lesions in 10% of cases, and cv lesions alone in 30%. The prognosis of the graft exhibiting CVR was not too poor even under the present immunosuppressive protocol.
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clinicopathologic analysis of acute Vascular Rejection cases after renal transplantation
Transplantation proceedings, 2012Co-Authors: Tomokazu Shimizu, Hideki Ishida, Kazuya Omoto, Tatsu Tanabe, Kazunari TanabeAbstract:Abstract Introduction Histopathologic change of acute Vascular Rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. Patients AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. Results Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2–t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated Rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant Rejection (SRR) requiring greater anti-Rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. Conclusions In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.
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clinicopathological analysis of acute Vascular Rejection cases after renal transplantation
Clinical Transplantation, 2010Co-Authors: Tomokazu Shimizu, T Tokumoto, Kuniko Tsunoyama, Hideki Ishida, H Shirakawa, Kazuya Omoto, Kazunari TanabeAbstract:Shimizu T, Ishida H, Shirakawa H, Omoto K, Tsunoyama K, Tokumoto T, Tanabe K. Clinicopathological analysis of acute Vascular Rejection cases after renal transplantation. Clin Transplant 2010: 24 (Suppl. 22): 22–26. © 2010 John Wiley & Sons A/S. Abstract: Histopathological change of acute Vascular Rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathological analysis of AVR cases after renal transplantation (RTX). Patients: AVR was diagnosed in 17 patients from 17 renal transplant patients followed in our institute between January 2003 and September 2008. We retrospectively reviewed these 17 patients. Results: Among 17 cases of AVR, 10 cases were mild (v1 in Banff 07 classification), five were moderate (v2), and two were severe (v3). Interstitial inflammation (i1–i3) was present in all 17 biopsies. Moderate to severe tubulitis (t2–t3) was present in seven biopsies, and transplant glomerulitis (g1–g3) was present in 11, peritubular capillaritis (ptc1–ptc3) was in 15 of 17 biopsies. C4d deposition in peritubular capillary (PTC) was observed in 6 of 17 cases. By assaying with plastic beads coated with anti-human leukocyte antigen (HLA) antigen performed in 17 cases, the circulating ant-HLA alloantibody was detected in 10 patients, of which 5/10 were donor-specific antibodies (DSA). Acute antibody-mediated Rejection (AAMR) was diagnosed in three cases. Many of v1 cases, steroid pulse therapy (SP) were effective. In v2 and v3 cases, six of seven were steroid-resistant Rejection and were need more anti-Rejection therapy (ART), such as muromonab CD3 (OKT3) injection, gusperimus (DSG) injection, plasmapheresis, intravenous immune globulin, and injection of rituximab. Ten of 17 patients recovered their renal allograft functions by ART, and 16 of 17 patients’ grafts are functioning. Deterioration of renal allografts’ function after biopsies was seen in seven patients with one of them lost their graft. Conclusions: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good in present immunosuppression and ART.
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Clinicopathological analysis of acute Vascular Rejection cases after renal transplantation.
Clinical transplantation, 2010Co-Authors: Tomokazu Shimizu, T Tokumoto, Kuniko Tsunoyama, Hideki Ishida, H Shirakawa, Kazuya Omoto, Kazunari TanabeAbstract:Histopathological change of acute Vascular Rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathological analysis of AVR cases after renal transplantation (RTX). AVR was diagnosed in 17 patients from 17 renal transplant patients followed in our institute between January 2003 and September 2008. We retrospectively reviewed these 17 patients. Among 17 cases of AVR, 10 cases were mild (v1 in Banff 07 classification), five were moderate (v2), and two were severe (v3). Interstitial inflammation (i1-i3) was present in all 17 biopsies. Moderate to severe tubulitis (t2-t3) was present in seven biopsies, and transplant glomerulitis (g1-g3) was present in 11, peritubular capillaritis (ptc1-ptc3) was in 15 of 17 biopsies. C4d deposition in peritubular capillary (PTC) was observed in 6 of 17 cases. By assaying with plastic beads coated with anti-human leukocyte antigen (HLA) antigen performed in 17 cases, the circulating ant-HLA alloantibody was detected in 10 patients, of which 5/10 were donor-specific antibodies (DSA). Acute antibody-mediated Rejection (AAMR) was diagnosed in three cases. Many of v1 cases, steroid pulse therapy (SP) were effective. In v2 and v3 cases, six of seven were steroid-resistant Rejection and were need more anti-Rejection therapy (ART), such as muromonab CD3 (OKT3) injection, gusperimus (DSG) injection, plasmapheresis, intravenous immune globulin, and injection of rituximab. Ten of 17 patients recovered their renal allograft functions by ART, and 16 of 17 patients' grafts are functioning. Deterioration of renal allografts' function after biopsies was seen in seven patients with one of them lost their graft. In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good in present immunosuppression and ART.
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a case of acute Vascular Rejection after overseas deceased kidney transplantation
Clinical Transplantation, 2007Co-Authors: Tomokazu Shimizu, Kazunari Tanabe, T Tokumoto, Kuniko Tsunoyama, Hideki Ishida, Hiroshi Kobayashi, Kentaro Masumoto, Junpei Iizuka, Shun Ichi Kajimoto, Yutaka YamaguchiAbstract:A 54-yr-old Japanese male received overseas deceased kidney transplantation in January 2006. His allograft functioned immediately and he received immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), and prednisone (PR). On day 24 after transplantation, he came back to Japan. His serum creatinine level (s-Cr) was 1.39 mg/dL at two months after transplantation when he was admitted into Toda Central General Hospital on March 2006, for follow-up his renal allograft. He had taken only two immunosuppressive drugs, MMF and PR, and had not taken CyA at that time. His serum creatinine gradually rose after hospitalization. Allograft biopsy performed on April 6, 2006, showed acute Vascular Rejection (Banff 97 acute/active cellular Rejection Grade III), together with suspicious for acute humoral Rejection (Banff 97 antibody-mediated Rejection Grade II). After treatment of two courses of steroid pulses and five d of gusperimus, acute Vascular Rejection and acute humoral Rejection were relieved, which had been proven by the third allograft biopsy. In conclusion, this was a case of acute Vascular Rejection after overseas deceased kidney transplantation, resulted from non-compliance with immunosuppressive therapy.
Jeanpaul Dehoux - One of the best experts on this subject based on the ideXlab platform.
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characterization of baboon anti porcine igg antibodies during acute Vascular Rejection of porcine kidney xenograft
Xenotransplantation, 2002Co-Authors: Jeanpaul Dehoux, Bernardo De La Parra, Dominique Latinne, Herve Bazin, Pierre GianelloAbstract:In the pig-to-baboon model, the removal of anti-porcine natural antibodies abrogates hyperacute Vascular Rejection (HAVR), but the xenograft then undergoes an acute Vascular Rejection (AVR) concomitantly to the appearance of newly formed anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim of this work was to characterize the anti-porcine antibodies during AVR. Sera from anti-IgM-treated animals were assessed prior to the graft and at the time of AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine antibodies concentration as well as the IgG subtypes. The same sera were tested on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i) the cytolytic complement-dependent activity and (ii) the E-selectin expression. The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to discriminate the presence of Gal epitopes from the recognition of other porcine epitopes. We found that both anti-porcine IgM and IgG antibodies presented a significantly increased cytolytic activity and E-selectin expression on PAECs during AVR. These characteristics are related to an important increase of the antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl IgG1 subclass production, whereas the K affinity remained unchanged. The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies.
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Characterization of baboon anti‐porcine IgG antibodies during acute Vascular Rejection of porcine kidney xenograft
Xenotransplantation, 2002Co-Authors: Jeanpaul Dehoux, Bernardo De La Parra, Dominique Latinne, Herve Bazin, Pierre GianelloAbstract:In the pig-to-baboon model, the removal of anti-porcine natural antibodies abrogates hyperacute Vascular Rejection (HAVR), but the xenograft then undergoes an acute Vascular Rejection (AVR) concomitantly to the appearance of newly formed anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim of this work was to characterize the anti-porcine antibodies during AVR. Sera from anti-IgM-treated animals were assessed prior to the graft and at the time of AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine antibodies concentration as well as the IgG subtypes. The same sera were tested on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i) the cytolytic complement-dependent activity and (ii) the E-selectin expression. The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to discriminate the presence of Gal epitopes from the recognition of other porcine epitopes. We found that both anti-porcine IgM and IgG antibodies presented a significantly increased cytolytic activity and E-selectin expression on PAECs during AVR. These characteristics are related to an important increase of the antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl IgG1 subclass production, whereas the K affinity remained unchanged. The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies.
Simon C. Robson - One of the best experts on this subject based on the ideXlab platform.
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acute Vascular Rejection of xenografts roles of natural and elicited xenoreactive antibodies in activation of Vascular endothelial cells and induction of procoagulant activity
Transplantation, 2004Co-Authors: Bernd Gollackner, David K C Cooper, Imrana Qawi, L Buhler, Christoph Knosalla, Soizic Daniel, Elzbieta Kaczmarek, M Awwad, Simon C. RobsonAbstract:Hyperacute Rejection of Vascularized discordant xenografts can now be effectively managed. However, acute Vascular Rejection (AVR) then ensues, resulting in graft destruction, coagulopathy, or both within weeks. The aim of this study was to determine associations between humoral responses to the xenograft and the induction of AVR, coagulopathy, or both.
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acute Vascular Rejection delayed xenograft Rejection and consumptive coagulopathy in xenotransplantation
Current Opinion in Organ Transplantation, 2003Co-Authors: Simon C. RobsonAbstract:Hyperacute Rejection of Vascularized discordant xenografts is induced by natural antibodies and mediated by complement and associated coagulation factor activation. This immediate Rejection process can now be effectively managed by complement inhibition. However, acute Vascular Rejection or delayed xenograft Rejection then ensues and can result in destruction of the organ within days to weeks. This form of Rejection is associated with Vascular inflammation, thrombocytopenia, and the consumption of coagulation factors. Primary biologic incompatibilities of the xenograft with respect to regulation of clotting could further amplify this process. Additionally, infection of the xenograft Vascular endothelium by cytomegalovirus or other pathogens may cause severe Vascular injury. Interventions with standard and novel anticoagulant/antithrombotic therapies in a systemic or targeted manner should have beneficial effects with respect to prolongation of xenograft survival. This article focuses on the progress that has been made toward the understanding of the coagulation disturbances accompanying xenotransplantation.
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Acute Vascular Rejection/delayed xenograft Rejection and consumptive coagulopathy in xenotransplantation
Current Opinion in Organ Transplantation, 2003Co-Authors: Simon C. RobsonAbstract:Hyperacute Rejection of Vascularized discordant xenografts is induced by natural antibodies and mediated by complement and associated coagulation factor activation. This immediate Rejection process can now be effectively managed by complement inhibition. However, acute Vascular Rejection or delayed xenograft Rejection then ensues and can result in destruction of the organ within days to weeks. This form of Rejection is associated with Vascular inflammation, thrombocytopenia, and the consumption of coagulation factors. Primary biologic incompatibilities of the xenograft with respect to regulation of clotting could further amplify this process. Additionally, infection of the xenograft Vascular endothelium by cytomegalovirus or other pathogens may cause severe Vascular injury. Interventions with standard and novel anticoagulant/antithrombotic therapies in a systemic or targeted manner should have beneficial effects with respect to prolongation of xenograft survival. This article focuses on the progress that has been made toward the understanding of the coagulation disturbances accompanying xenotransplantation.
