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alloantibodies and infection recipient transplantation

Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
BACKGROUND: The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus, a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, tacrolimus-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed...
May 19, 2018: Expert Review of Clinical Pharmacology
Martin Schweiger, Andreas Zuckermann, Andres Beiras-Fernandez, Michael Berchtolld-Herz, Udo Boeken, Jens Garbade, Stephan Hirt, Manfred Richter, Arjang Ruhpawar, Jan Dieter Schmitto, Felix Schönrath, Rene Schramm, Uwe Schulz, Markus J Wilhelm, Markus J Barten
Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy in this special population are far less extensive than for adults. Induction is used more widely in pHTx than in adults, mainly because of early steroid withdrawal or complete steroid avoidance. Antithymocyte globulin (ATG) is the most frequent choice for induction in pHTx, and rabbit antithymocyte globulin (rATG, Thymoglobulin®) (Sanofi Genzyme) is the most widely-used ATG preparation...
May 15, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Feifei Qiu, Huazhen Liu, Chun-Ling Liang, Golay D Nie, Zhenhua Dai
Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity...
2017: Frontiers in Immunology
Miguel López-Botet, Carlos Vilches, Dolores Redondo-Pachón, Aura Muntasell, Aldi Pupuleku, José Yélamos, Julio Pascual, Marta Crespo
Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection...
2017: Frontiers in Immunology
Lionel Rostaing, Béatrice Karam, Nicolas Congy-Jolivet, Valérie Hage, Federico Sallusto, Laure Esposito, Nicolas Doumerc, Bénédicte Debiol, Céline Guilbeau-Frugier, Xavier Game, Asma Allal, Nassim Kamar
Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m(2) ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption)...
October 2016: Therapeutic Apheresis and Dialysis
Kaan Gulleroglu, Esra Baskin, Gokhan Moray, Handan Ozdemir, Hande Arslan, Mehmet Haberal
OBJECTIVES: Rituximab is a monoclonal antibody directed against the CD20 molecule on pre-B and mature B cells and is used in transplant recipients for the prevention and treatment of alloantibody-mediated rejection or for the treatment of disease recurrence after transplant. In most patients, rituximab has been safe and well-tolerated, but the long-term adverse effects of rituximab are currently unknown. MATERIALS AND METHODS: We retrospectively evaluated 78 pediatric renal transplant recipients for the occurrence of infectious disease...
April 2016: Experimental and Clinical Transplantation
Alexander J Hamilton, Lynsey H Webb, Jennifer K Williams, Richard J D'Souza, Loretta S P Ngu, Jason Moore
BACKGROUND: Autoimmune haemolytic anaemia (AIHA) is a rare complication following kidney transplantation and usually occurs early in its course. It is characterised by autoantibodies or alloantibodies directed against red blood cells (RBCs). CASE PRESENTATION: We describe a 44 year old woman who presented 5 years after kidney transplantation with profound transfusion dependent warm AIHA. Investigations confirmed an IgG autoantibody against RBCs and high titre Epstein-Barr virus (EBV) viraemia...
2015: BMC Nephrology
Tülay Kılıçaslan Ayna, Yaşar Calışkan, Hayriye Şentürk Ciftçi, Aydın Türkmen, Mehmet Gürtekin
OBJECTIVE: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA)-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients. STUDY DESIGN: Prospective follow-up study. MATERIAL AND METHODS: A total of 56 kidney recipients were monitored at 1(st), 6(th) and 12(th) months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests)...
March 2013: Balkan Medical Journal
Jacqueline G O'Leary, Hugo Kaneku, Linda Jennings, Brian M Susskind, Paul I Terasaki, Göran B Klintmalm
Hepatitis C virus (HCV) fibrosis progression after liver transplantation (LT) is accelerated in comparison with fibrosis progression before transplantation. The vast majority of the risk factors for fibrosis progression after LT are not modifiable. With the goal of identifying modifiable risk factors for fibrosis progression, we evaluated the impact of preformed and de novo donor-specific human leukocyte antigen alloantibodies (DSAs) on fibrosis progression after LT in HCV-viremic patients. After blinding, we analyzed all 507 HCV-viremic patients who underwent primary LT from January 2000 to May 2009 and had pretransplant and posttransplant samples available for analysis (86% of the total) for preformed and de novo class I and class II DSAs with a mean fluorescence intensity ≥ 5000 with single-antigen bead technology...
June 2014: Liver Transplantation
Yvon Lebranchu, Carla Baan, Luigi Biancone, Christophe Legendre, José Maria Morales, Maarten Naesens, Oliver Thomusch, Peter Friend
Lack of an accepted definition for 'high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient-related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor...
February 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
Matthew J Everly
The purpose of immunosuppression in patients receiving a solid organ transplant is to prevent both acute and chronic rejection, while avoiding the complications of immunodeficiency such as infections and malignancy. Over the last 50 years, immunosuppressive agents have been developed and put into clinical practice to achieve this purpose. The majority of immunosuppressive agents developed during this time have focused on suppressing the T cells. T cell centric immunosuppressive development was a result of the early belief that the T cell caused an allograft to fail...
2012: Clinical Transplants
T Fairhead, E Hendren, K Tinckam, C Rose, C H Sherlock, L Shi, N S Crowcroft, J B Gubbay, D Landsberg, G Knoll, J Gill, D Kumar
BACKGROUND: Seasonal and pandemic influenza virus infections in renal transplant patients are associated with poor outcomes. During the pandemic of 2009-2010, the AS03-adjuvanted monovalent H1N1 influenza vaccine was recommended for transplant recipients, although its immunogenicity in this population was unknown. We sought to determine the safety and immunogenicity of an adjuvant-containing vaccine against pandemic influenza A H1N1 2009 (pH1N1) administered to kidney transplant recipients...
December 2012: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Saurabh Zalpuri, Jaap Jan Zwaginga, J G van der Bom
INTRODUCTION: Individuals exposed to red blood cell alloantigens through transfusion, pregnancy or transplantation may produce antibodies against the alloantigens. Alloantibodies can pose serious clinical problems such as delayed haemolytic reactions and logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected. OBJECTIVE: The authors hypothesise that the particular clinical conditions (eg, used medication, concomitant infection, cellular immunity) during which transfusions are given may contribute to the risk of immunisation...
2012: BMJ Open
Cyril Garrouste, Nassim Kamar, Céline Guilbeau-Frugier, Joëlle Guitard, Laure Esposito, Laurence Lavayssière, Marie-Béatrice Nogier, Olivier Cointault, David Ribes, Lionel Rostaing
OBJECTIVES: This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients. MATERIALS AND METHODS: From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant. RESULTS: After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus...
April 2012: Experimental and Clinical Transplantation
Jun Li, Gang Chen, Ping Ye, Sihua Wang, Kailun Zhang, Wenhao Chen, Stanislaw M Stepkowski, Junhua Li, Shan Zhong, Jiahong Xia
Maraviroc (MVC), a specific antagonist of CCR5 expressed on macrophages and activated T cells, may modulate inflammation and may be useful in patients with HIV infection. In this study we used nonhuman primates to examine the effect and mechanism of MVC alone or in combination with cyclosporine (CsA) to prolong cardiac allograft survivals. In an established rhesus monkey cardiac allograft model, recipients treated with MVC plus CsA showed significantly prolonged survival of heart allografts (>240 d, p < 0...
March 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Eleftherios C Vamvakas, Morris A Blajchman
After reviewing the relative frequency of the causes of allogeneic blood transfusion-related mortality in the United States today, we present 6 possible strategies for further reducing such transfusion-related mortality. These are (1) avoidance of unnecessary transfusions through the use of evidence-based transfusion guidelines, to reduce potentially fatal (infectious as well as noninfectious) transfusion complications; (2) reduction in the risk of transfusion-related acute lung injury in recipients of platelet transfusions through the use of single-donor platelets collected from male donors, or female donors without a history of pregnancy or who have been shown not to have white blood cell (WBC) antibodies; (3) prevention of hemolytic transfusion reactions through the augmentation of patient identification procedures by the addition of information technologies, as well as through the prevention of additional red blood cell alloantibody formation in patients who are likely to need multiple transfusions in the future; (4) avoidance of pooled blood products (such as pooled whole blood-derived platelets) to reduce the risk of transmission of emerging transfusion-transmitted infections (TTIs) and the residual risk from known TTIs (especially transfusion-associated sepsis [TAS]); (5) WBC reduction of cellular blood components administered in cardiac surgery to prevent the poorly understood increased mortality seen in cardiac surgery patients in association with the receipt of non-WBC-reduced (compared with WBC-reduced) transfusion; and (6) pathogen reduction of platelet and plasma components to prevent the transfusion transmission of most emerging, potentially fatal TTIs and the residual risk of known TTIs (especially TAS)...
April 2010: Transfusion Medicine Reviews
Malek Kamoun
This review was designed to highlight new findings that have contributed to our knowledge of the pathogenesis of late graft dysfunction. Both immune and nonimmune causes contribute to its development. Specific contributors to late graft dysfunction have been recently recognized and are potential targets for new treatment options. The variables associated with late graft failure include donor age and tissue quality, brain death and other issues specific to the deceased donor, tissue injury secondary to organ preservation, alloimmune-mediated injury, and posttransplantation factors in the recipient, such as viral infections, hypertension, drug toxicity, and hyperlipidemia...
February 2006: Therapeutic Drug Monitoring
Irma H Matinlauri, Lauri E J Kyllönen, Björn H Eklund, Saija A Koskimies, Kaija T Salmela
BACKGROUND: Screening of donor-specific antibodies or alloantibodies after kidney transplantation has not been performed routinely. The aim of this study was to evaluate the humoral antidonor and alloresponse of immunologically low-risk recipients of cadaveric renal allografts during the first posttransplant year. METHODS: Alloresponse against the donor was analyzed by means of T-cell immunoglobulin (Ig)G and IgM and B cell IgG flow cytometric crossmatch (FCXM) tests with sera from days 0, 21, 90, and 365 posttransplant...
July 27, 2004: Transplantation
Frans H J Claas, Marian D Witvliet, René J Duquesnoy, Guido G Persijn, Ilias I N Doxiadis
There are many highly sensitized patients on the kidney waiting lists of organ exchange organizations because it is difficult to find a crossmatch negative cadaver kidney for these patients. Recently, several protocols have been developed to remove the donor-specific human leukocyte antigen (HLA) antibodies from the serum of these patients before transplantation. These approaches, including the use of intravenous immunoglobulins, plasmapheresis and immunoglobulins (plasmapheresis-cytomegalovirus-immunoglobulin), and immunoabsorption, seem to lead to a certain success rate, although the additional immunosuppression necessary to remove and control the production of donor-specific alloantibodies may have its impact on the short-term (infections) and long-term (incidence of cancer) immune surveillance...
July 27, 2004: Transplantation
Masaomi Yamane, Yoshifumi Sano, Nobuyoshi Shimizu
BACKGROUND: The diagnosis of acute rejection after organ transplantation is often complicated by other possibilities, such as infection. Despite many attempts to identify rejection episodes after transplantation, only the detection of the humoral anti-human leukocyte antigen antibody has been effective in measuring alloimmunization, especially detected with flow cytometry cross-match (FCXM). As an initial step towards gaining a better understanding of the correlation between humoral responses and graft rejection in an immunosuppressant recipient, we investigated responses of alloantibodies (allo-Abs) after lung transplantation (LTx) in a rat model treated with adequate or inadequate cyclosporine A (CsA) therapy...
January 2004: Transplant Immunology
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