Background Cytokine storm described in patients after allogeneic haematopoietic stem cell transplantation (alloHSCT) is associated with the appearance of CD14 + HLADR - in the blood. Methods To study the role of CD14 + HLADR - cells 223 patients after alloHSCT followed from 1 month to 15 years. The methods used included flow cytometry for blood cells profiling, nucleic acid tests for viral reactivation

Background: The reduced access of highly-sensitized (HS) patients to kidney transplantation (KTx) is one of the major challenges for transplant community. Therefore, the aim of our study was to estimate the impact of three different vPRA calculations, assessed traditionally and using eplet-based analysis, in donor offers. Methods: At 01-01-2020, 157 HS patients are waitlisted for deceased donor KTx

Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effect of rituximab on the T-FCXM using non-pronase and pronase treated donor lymphocytes

Background Numerous studies suggest that cytomegalovirus (CMV) infection may act as isolated risk factor in the development of cardiac allograft vasculopathy (CAV). Viral G protein-coupled receptors (GPCRs) are thought to contribute to the pathogenic changes associated with CMV infection. The aim of this study was to investigate the role of murine cytomegalovirus GPCR M33 in the development of CAV

Background Donor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose. Methods A post-preservation flush was performed with STEEN solution in

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait

Background Mycophenolate mofetil (MMF), an immunosuppressive drug, exerts anti-inflammatory effects on organs during ischemia/reperfusion (I/R) injury. However, the exact function of MMF in hepatic I/R injury remains largely unknown. The purpose of this study was to explore the role and potential mechanism of MMF protection in hepatic I/R injury. Methods Male wild type (WT) and TLR4 knockout (KO) mice

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 manifestations, have a high prevalence but are rarely studied. We analyzed these manifestations'

In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-alveolar lavage (BAL) of lung transplant patients with diverse post-transplant complications

Corneal transplantation rejection remains an urgent problem threatening the success rate of high-risk patients. Macrophages are involved in the rejection of corneal transplants. Macrophages have M1 and M2 phenotypes, classified according their response to external stimuli. Macrophage polarization, through which these distinct forms are activated, is not only involved in the occurrence and development

Background Allogeneic transplantation immune tolerance is currently a hot research issue and soluble CD83(sCD83) is a novel immunomodulator with great potential in inducing transplantation tolerance. Objective To investigate the mechanism of the immune tolerance effect of sCD83 on rat liver transplantation. Method A rat liver transplantation model was established to study the effects of sCD83 on the

Introduction Detection of donor specific antibodies (DSA) is critical in both solid organ and mismatched haematopoetic stem cell transplants. The single antigen bead assay (SAB) is widely used as a virtual crossmatch in these settings. However, HLA allele variation across ethnicities and differing genetic backgrounds is a well-known and acknowledged fact and representation of alleles prevalent in a

We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative

Massive Open Online Courses (MOOCs) offer an entirely new course concept for delivering content and engaging learners. This method of teaching has huge potential for the field of transplant education. In this study we describe the development and implementation of the MOOC “Clinical Kidney, Pancreas and Islet Transplantation”. Three and a half years after the introduction of the course, the learning

The Fingolimod (FTY720, Gilenya) is clinically approved for the treatment of multiple sclerosis (MS). Its therapeutic effect on MS is based on the ability to bind sphingosine 1-phosphate (S1P) receptors and block the exit of immune cells from the lymphoid organs, thus preventing immune cell-dependent injury to the central nervous system (CNS). We showed recently that, besides the S1P-related activity

Pattern recognition receptors (PRRs) trigger adaptive inflammatory responses and as such are attractive targets for therapeutic manipulation of inflammation. In order to develop effective therapies however we need to understand the complexities of PRR signaling and clarify how individual PRRs contribute to an inflammatory response in a given cell type. Data from our lab and others have shown that cross-talk

Introduction Recent studies suggested potential positive correlations between HLA-specific antibodies and development of cardiac allograft vasculopathy (CAV). Methods This prospective two-center study investigated early progression of CAV by coronary optical coherence tomography in 1 month and 12 months after heart transplantation (HTx) in 104 patients. Detection and characterization of donor specific

We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination

Uterine transplantation (UTx) is the only effective treatment for uterine infertility patients to become genetic mothers. After decades of research, the surgical methods of UTx are very developed. There are numerous factors that affect the results of UTx, such as selection of the donor uterus before transplantation, immunosuppressive therapy post-transplantation, rejection monitoring, and immune tolerance

Aim To study the release mechanism of C-X-C motif chemokine 11 (CXCL11) and other chemokines after the co-cultivation of CD4+ and CD8+ T cells with the renal tubular epithelial cells (RTEC) in the process of allograft renal transplantation rejection. Methods The Human CD4+, CD8+ T cells were obtained from the blood of volunteers and kidney transplantation (Ktx) patients, and co-cultured with renal

Recently the role of metabolic signaling pathways has emerged as playing a critical role in dictating the outcome of T cell responses. The uptake and metabolism of the amino acid glutamine is essential for effector T cell activation. Since the growth and expansion of tumor cells relies on similar anabolic and metabolic requirements, we hypothesized that glutamine blockage might represent a promising

Introduction Antibody mediated rejection is the leading cause of kidney transplant failure. Not all antibodies are harmful and some may be protective. Immunoglulin Gs, of which there are four subtypes, are detected by single antigen bead testing. The aims of this study were to characterise the IgG subclass profiles for class I HLA-specific antibodies in an uncensored post-transplant population and

Background Donor-specific antibodies (DSAs) have various negative short- and long-term effects after organ transplantation. DSAs are prevalent in patients with insufficient immunosuppression; thus, even patients with stable conditions after liver transplantation should be under optimized immunosuppression. However, the effect of re-augmenting immunosuppression therapy for patients with insufficient

Background Anti-HLA immunization determined by Panel Reactive Antibody (PRA) is known to have a negative impact on patient and graft survival. The predictive value of peak PRA (pPRA) on immunologic outcome, however, and the individual effects of anti-HLA class I and II antibodies remain uncertain. Methods The influence of HLA immunization on immunologic outcome parameters and graft survival was investigated

Innate immune reactions are believed to be associated with ischemia/reperfusion injury (IRI), and IRI might be treatable by expanding regulatory T cells (Tregs), which can suppress the excessive responses of the immune system. Organ IRI is known to be closely involved in the expression of costimulatory molecules. The present study aimed to assess whether Tregs endogenously expanded by the administration

Ischemia-reperfusion (I/R) injury, an inevitable result of kidney transplantation, triggers early inflammatory events that affect graft viability. Evidence from human transplantation and preclinical models of I/R suggests that a female hormonal environment positively influences the ability to recover from ischemic injury. However, the mechanisms behind these effects remain mostly unexplored. Here,

Objectives Islet transplantation has been proved to be effective in delaying early stage of DN. This study was established to observe the mechanism of islet transplantation on early diabetic nephropathy (DN). Method The diabetes mellitus (DM) rat model was established by an injection of a single-dose streptozotocin. According to the treatment, the rats were randomly divided into 4 groups: the untreated

Background The presence of neutrophils in the lung was identified as a factor associated with CLAD but requires invasive samples. The aim of this study was to assess the kinetics of peripheral blood neutrophils after lung transplantation as early predictor of CLAD. Methods We retrospectively included all recipients transplanted in our center between 2009 and 2014. Kinetics of blood neutrophils were

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. Materials and methods TLR4ex was measured in peripheral blood mononuclear cells of 43

Objective Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined. Methods In this study, we established a mouse-to-mouse cardiac transplantation model and identified

Background The inclusion of compatible pairs within kidney paired exchange programs has been described as a way to enhance these programs. Improved immunological matching for the recipient in compatible pair has been described to be a possible benefit. Methods The main purpose of our study was to determine if the introduction of compatible pairs in the Portuguese kidney paired exchange program would

This study provides data on HLA-A, -B, and -DRB1 frequencies among 861 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadaveric donors (422 from Croatia and 285 from Eurotransplant). Patients positive for

Introduction Single antigen bead testing (SAB) for HLA-specific antibody enables efficient organ allocation and aids in the diagnosis of antibody mediated rejection. In this retrospective cohort study, a population of kidney transplant recipients possessing HLA Class I antibodies was used to evaluate the best method for resolving complement interference, the so called “prozone” effect. The aim was

Guy Alexandre made major contributions to organ transplantation that, in my opinion, have not been sufficiently recognized by the transplant community. To make his contributions better known, I present a brief summary of the innovations for which he was largely responsible. As a research fellow at the Peter Bent Brigham Hospital in Boston in 1962–3, under subsequent Nobelist Joseph Murray, he contributed

Objective: This study aims to summarize a clinical experience on the diagnosis and treatment of acute graft-versus-host disease (aGVHD) after liver transplantation. Methods: Between April 2005 and August 2016, 11 recipients who underwent OLT developed aGVHD with clinical symptoms of fever, rash, diarrhea and pancytopenia. T lymphocyte chimerism was detected though STR-PCR. These patients were treated

Background Vascularized composite allotransplantation (VCA) is a novel and life-enhancing procedure to restore a patient's function and/or appearance. Current immunosuppression in VCA recipients is based on calcineurin inhibitor (CNI) therapy that can lead to severe complications, such that inducing immune tolerance is a major goal of VCA research. In contrast to CNI, rapamycin (RPM) is thought to

Production of de novo DSA (dnDSA) is associated with an increased risk of antibody mediated rejection after liver transplantation. Antibodies not only recognize the entire antigen but are able to bind specific functional epitopes present on the HLA molecule surface. The HLAMatchmaker and the PIRCHE-II (predicted indirectly recognizable HLA epitopes) algorithms are able to determine predictive epitope

Achievement of complete donor chimerism after an allogeneic hematopoietic stem cell transplant is necessary for elimination of underlying malignant disease. A decline in donor chimerism may herald an impending relapse and therefore, early recognition and intervention plays an important role in such cases. A 32 year old male patient diagnosed as a case of Philadelphia positive mixed phenotypic acute

Introduction The appearance of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) after kidney transplantation is independently associated with poor long-term allograft outcomes. The objective of the present study was to evaluate the predictive value of a flow cytometry crossmatching (FC-XM) assay after the appearance of dnDSAs related to antibody-mediated allograft rejection (ABMR)

The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with

Belatacept, Nulojix®, inhibits the interaction of CD28 on naïve T cells with B7.1/B7.2 (CD80/86) on antigen presenting cells, leading to T cell hyporesponsiveness and anergy and is approved as immunosuppressive drug in kidney transplantation. Due to its specificity for B7.1/2 molecules, side effects are reduced compared to other immunosuppressive drugs like calcineurin- and mTOR-inhibitors. Kidney

Background The component (C3) of the complement system constitutes a central element in liver transplantation. C3 is produced mainly by the liver and comprises both slow (C3-S), and fast (C3-F) components. Methods The effect of a single nucleotide variation in the C3 gene on the first-year outcome examined by ARMS PCR in 30 recipients of living donor allograft. Results Frequencies of C3-S and C3-F

BACKGROUND The liver and renal capsule are the most common site for experimental pancreatic islet transplantation, but it is not optimal. Gastric submucosa space may be an ideal site for islet transplantation; however, whether pro-inflammation factors mediated islet dysfunction could be avoided or alleviated is still unclear. METHODS Islets of Sprague Dawley (SD) rat were transplanted into the streptozotocin-induced

Granzyme B is known to be a serine protease contained in granules of cytotoxic T cells. We have previously reported an influence of granzyme B expression in T regulatory cells (Tregs) on the risk of acute graft versus host disease (GVHD) onset. However, it is still unknown if conventional T cells (Tcon) use the granzyme B pathway as a mechanism of alloimmunity. We hypothesized that granzyme B in Tcon

Background It was found that regulatory T cells (Tregs) importantly affect the maintenance of the kidney graft. However, Tregs are a heterogeneous population with less to more suppressive activity. The aim of this study was to determine the effects of different subsets of Tregs, as well as their ratio to effector T cells (Teff), on kidney transplantation outcomes. Methods A total of 58 participants

Chronic kidney disease stage 5 (CKD5) dialysis patients who stay long term in uremic environment often exhibit several, poorly defined, immune impairments. In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in

Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing these consequences, the functional axis between the innate lymphoid cell subpopulation 3 (ILC3) and interleukin

BACKGROUND The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA. METHODS From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP

Background The aim of this study was to evaluate neutrophil extracellular traps (NETs) in kidney transplant recipients (KTR) and their potential involvement in acute antibody-mediated rejection (AAMR). Methods We studied 3 groups: KTR with AAMR (KTR-Cases, n = 14); KTR without any immunologic event (KTR-Controls, n = 14) and donors (n = 12). Spontaneous and lipopolysaccharide-induced NETosis were evaluated

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established

Long term survival post lung transplantation (LTx) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). One mechanism involved is the epithelial-mesenchymal transition (EMT). Membrane microparticles (MPs) are known to be involved in some respiratory diseases and in other organs allograft rejection episodes. We hypothesized that leukocyte-derived MPs likely contribute to EMT. To

The PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) score is an HLA epitope matching algorithm. PIRCHE algorithm estimates the level of presence of T-cell epitopes in mismatched HLA. The PIRCHE-II numbers associate with de novo donor-specific antibody (dnDSA) formation following liver transplantation and kidney allograft survival following renal transplantation. The aim of our study was to

Background Primary graft Dysfunction (PGD) results in significant mortality and morbidity after lung transplantation (LT). The objective of this study was to evaluate if pre-existing antibodies to self-antigens in sera of LT recipients are associated with PGD. Methods The serum profiles of IgG and IgA autoantibodies were analyzed using a customized proteomic microarray bearing 124 autoantigens. Autoantibodies

Background Accelerated transplant rejection mediated by donor reactive memory T cells is another barrier to the induction of graft tolerance. The aim of this study was to investigate the immunosuppressing effects of vitamin D (1,25(OH)2D3), administered alone or in combination with a costimulatory blockade treatment, on rejection of secondary heart allografts in a mouse model. Methods Circular full-thickness

Renal ischemia-reperfusion (I/R) injury is closely associated with delayed graft function and poor long-term graft survival following transplantation. Various pathophysiologies can cause the deterioration of renal function; however, the immune system plays important roles in promoting and protecting renal tissues. Receptor activator of NFκB ligand (RANKL) is a member of the TNF superfamily and is produced

We prospectively validated the previously reported L-index, which reflects both the intensity and duration of lymphopenia, and further evaluated it using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 30). The L-index was defined as the area over the lymphocyte curve during lymphopenia (<700/μl), and calculated from the start of conditioning to day30

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