Abstract:
BACKGROUND:B cell depletion by anti-CD20 antibody is used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). However, little is known about the efficacy and the mechanism(s) of action. METHODS:A mouse model of HLA sensitization was used to study the effectiveness of anti-CD20 treatment on B cell depletion and anti-HLA antibody suppression. RESULTS:Immunization of C57BL/6 mice with skin grafts from a transgenic C57BL.Tg/HLA-A2.1 mouse resulted in robust production of anti-HLA IgM and IgG antibodies, and accelerated rejection of a secondary skin allograft (within 3 days) featured by intragraft IgG and C4d deposition. Both IgM and IgG alloantibodies are specific to HLA-A2 as well as to a panel of class I HLA, including A1, A3, A25, A26, A29, and A30. These alloantibodies were complement-dependently cytotoxic (CDC) against HLA-A2 expressing target cells. Administration of 2 doses of a mouse-anti-mouse CD20 monoclonal antibody significantly reduced the levels of anti-HLA IgG2a antibodies, suppressed serum CDC, and prolonged survival of the secondary skin allografts. Suppression of anti-HLA IgG antibodies was associated with significant depletion of B220(+)/CD5(-) B cells from the blood, the spleen and the bone marrow of the treated animals. CONCLUSION:Anti-CD20 treatment effectively depletes B220(+)/CD5(-) B cells, resulting in potent suppression of anti-HLA IgG and prolongation of skin graft survival. The data are in support for the use of anti-CD20 antibodies in highly-HLA sensitized patients undergoing desensitization and for the treatment of AMR.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Wu GD,He Y,Chai NN,Toyoda M,Dunn R,Kehry MR,Klein AS,Jordan SCdoi
10.1016/j.trim.2008.05.004subject
Has Abstractpub_date
2008-07-01 00:00:00pages
178-86issue
3-4eissn
0966-3274issn
1878-5492pii
S0966-3274(08)00033-6journal_volume
19pub_type
杂志文章abstract::We present management strategies utilised for the first case of an urgent live-donor ABO incompatible B blood group renal transplant, in a patient with a prior A blood group lung transplant for cystic fibrosis. Three years on, renal function is excellent and stable, whilst lung function has improved. ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.09.002
更新日期:2016-11-01 00:00:00
abstract::The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immu...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/S0966-3274(03)00057-1
更新日期:2003-07-01 00:00:00
abstract::Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 po...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.001
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Ischemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive tr...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.10.006
更新日期:2011-01-15 00:00:00
abstract::We suggest that surveillance for squamous cell cancer might be particularly useful for transplant patients receiving statin therapy. We recommend that development of non melanoma skin cancer should be specified as a secondary endpoint in future large endpoint statin trials, and suggest that in transplant patients the ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.06.001
更新日期:2010-08-01 00:00:00
abstract:AIMS:Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a ra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.01.003
更新日期:2016-03-01 00:00:00
abstract::Type 1 diabetes is one of the more costly chronic diseases of children and adolescents throughout North America and Europe, exhibiting an average estimated prevalence rate of nearly 0.2%. It occurs in genetically predisposed individuals when the immune system attacks and destroys specifically the insulin-producing bet...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2003.12.011
更新日期:2004-04-01 00:00:00
abstract::The expression of CD30 is restricted to cells of the immune system and strictly regulated under physiological conditions. However, active immune cells express CD30 and soluble CD30 (sCD30) is released. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.07.001
更新日期:2010-08-01 00:00:00
abstract::Despite improvements in the prevention and treatment of graft-versus-host disease (GvHD) this allogeneic immune response is still one of major complications following allogeneic stem cell transplantation (SCT). Identification of patients at risk for the development of acute and chronic GvHD would facilitate early inte...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.07.003
更新日期:2012-12-01 00:00:00
abstract::In this review, we summarize the work published over the last few years relative to cellular immunological hurdles encountered specifically in pig-to-primate xenotransplantation models. The works summarized here cover both the innate and adaptative cellular immune response as well as strategies to overcome them and co...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2008.10.006
更新日期:2009-06-01 00:00:00
abstract::Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity is a major issue of long-term treatment. One method to improve such therapies is the application of immunomodulatory agents from parasites, such as Hypoderma lineatum (Diptera: Oestridae). Hypode...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.09.001
更新日期:2018-12-01 00:00:00
abstract::Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant rec...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.08.002
更新日期:2006-11-01 00:00:00
abstract::Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed wh...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(93)90059-h
更新日期:1993-01-01 00:00:00
abstract::FTY720 alters lymphocyte recirculation and homing by interfering with S1P receptors on lymphocytes, possibly in combination with chemokine receptors, and induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney transplant patients, we analyzed by flow cytometry the effect of FTY on the number of NK...
journal_title:Transplant immunology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.trim.2006.02.002
更新日期:2006-04-01 00:00:00
abstract::Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A,...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.02.005
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Results from published studies on the association of donor or recipient IL-6 -174G/C (rs1800795) polymorphism with acute rejection (AR) of renal allograft are conflicting. We performed a meta-analysis to estimate the possible association. METHODS:Studies were identified by searching PUBMED and EMBASE until ...
journal_title:Transplant immunology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.trim.2011.10.003
更新日期:2012-01-01 00:00:00
abstract::Upon activation, T cells express CD40L, a member of the TNF cytokine superfamily, which serves as a ligand for CD40 on antigen presenting cells, including dendritic cells, B cells, and macrophages. While initial studies on the function of CD40 focused its role in the regulation of B cell activation, more recent studie...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(00)00026-5
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.04.004
更新日期:2005-10-01 00:00:00
abstract::Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.09.006
更新日期:2014-01-01 00:00:00
abstract::B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.003
更新日期:2011-05-01 00:00:00
abstract::Previous work on the facilitation of xenogeneic and allogeneic bone marrow engraftment in irradiated mice and dogs with transferrins allowed the development of a model for induction of an apparently durable state of immunological unresponsiveness or 'tolerance' in chemically immunosuppressed mice. The system is based ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80051-7
更新日期:1996-12-01 00:00:00
abstract::Data binding the expression of Toll-like 4 receptor (TLR4ex), transplanted kidney function, and the cause of pre-transplant end-stage renal disease are scarcely available. OBJECTIVE:To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function. M...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101319
更新日期:2020-10-01 00:00:00
abstract::Experimental data show that relatively low concentrations of 15-deoxyspergualin (DSG) inhibit the induction of cytotoxic T lymphocytes (CTL) and the generation of antibody-producing cells. Considerably higher concentrations of DSG are required to inhibit proliferative responses. In this in vitro study, the effects of ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80007-4
更新日期:1996-06-01 00:00:00
abstract::Introduction of MHC class I Kb cDNA via recombinant retrovirus into B10.AKM (Kk) bone marrow cells (BMC) has been shown to confer specific hyporesponsiveness to B10.MBR (Kb) allogeneic skin grafts in lethally irradiated B10.AKM recipients of the transduced syngeneic BMC. We have recently developed a nonmyeloablative c...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80044-x
更新日期:1996-03-01 00:00:00
abstract::Adenoviral gene transfer is a potential ex vivo gene therapy for islet transplantation. However, the immunogenicity of adenoviral vectors can potentially impair vector efficacy in transplants where long-term gene expression is required. We investigated the effect of this antiviral immunity on vector expression and isl...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.02.001
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2019.101248
更新日期:2020-02-01 00:00:00
abstract::Humoral rejection and its relationship with anti HLA antibodies have been extensively studied in organ transplantation with the exception of liver transplantation (LT). Recently, association between donor specific anti HLA antibodies (DSA) and increased risk of rejection and graft loss has been suggested in LT. When s...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.01.007
更新日期:2016-03-01 00:00:00
abstract::Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifesta...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101355
更新日期:2021-02-01 00:00:00
abstract::Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.001
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:We recently reported that autoreactive antibody (Ab) against nuclear histone H1 had been identified as an immunosuppressive factor in a rat tolerogenic orthotopic liver transplantation (OLT) model. The present study aimed to determine whether the up-regulation of antihistone H1 Ab by histone H1 vaccination l...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.01.003
更新日期:2007-04-01 00:00:00