alloantibodies and infection recipient transplantation

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...

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...

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...

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...

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...

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...

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...

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)...

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...

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...

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...

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...

BACKGROUND: Organ transplant recipients currently require lifetime immunosuppressive therapy, with its accompanying side effects. Biological agents that block T-cell costimulatory pathways are important components of strategies being developed to induce transplantation tolerance. The aim of this study was to test the effect of a novel chimeric anti-human CD40 monoclonal antibody (Chi 220), either alone or in combination with CTLA4-Ig, on the survival of renal allografts in a nonhuman primate model...

Blood transfusions can induce both immune activation and immunosuppression. The former is expressed by the induction of HLA alloantibodies and T cell activation, while the latter is accompanied by enhanced graft survival in transfused versus non-transfused recipients. The immunological mechanism leading to downregulation of the alloimmune response has not yet been elucidated. Possible explanations include the induction of a Th2 response by non-professional antigen presentation by the transfused blood cells and blockage of alloreactive T cell reactivity by soluble HLA and soluble FasL in the supernatant of blood components...

HLA-specific humoral immunity, as a result of recipient allosensitization, induces hyperacute rejection of allogeneic kidney grafts. Cross-match tests are performed to avoid this complication. However, present techniques do not allow determination of HLA specificity of donor-reactive antibodies in the acute necro-donor situation. New methods are described and discussed in this communication as well as the alloantibody specificities which are of clinical importance. Alloantibodies not only mediate hyperacute rejection, but may also participate in the acute rejection of organ grafts...

Mouse bone marrow-derived myeloid dendritic cells (DC) propagated in granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta1 (TGF-beta1) (so-called 'TGF-beta DC') are phenotypically immature, and prolong allograft survival. Interleukin-10 (IL-10) has been shown to inhibit the maturation of DC by down-regulating surface major histocompatibility complex (MHC) class II, co-stimulatory and adhesion molecule expression. Genetic engineering of TGF-beta DC to overexpress IL-10 might enhance their tolerogenic potential...

BACKGROUND: We have previously shown that >75% of LEW cardiac allografts survive indefinitely in BUF rats pretreated at Day -21 intrathymically (IT) with donor alloantigen in conjunction with a single intravenous dose of ALS. Spleen cells can adoptively transfer the tolerant state to new cohorts of test recipients. This study was designed to analyze cellular and humoral events contributing to the "infectious" tolerance pathway in this model. METHODS: Spleen cells (25 x 10(6)) harvested from BUF recipients bearing long-term cardiac allografts were injected intravenously into lightly irradiated (450 R) secondary BUF rats, followed 24 h later by transplantation of LEW of ACl hearts...

Our unit was established in 1972 as Laboratory of Clinical Immunology in the Department of Nephrology, Medical Academy, Sofia Since 1985 it was expanded in Division of Clinical and Transplantation Immunology. Transplantation activity includes: HLA typing (serology and DNA) of all kind of recipients and donors, alloantibody screening and crossmatching (basic microlymphocytotoxicity, DTT and flowcytometry tests). Immunologic evaluation of patients prior to and after transplantation is also performed for individualization of immunosuppressive therapy and discrimination between rejection, CMV infection and cyclosporine toxicity...

BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR. METHODS: Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR...

Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir...