Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients.

Introduction: Immunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic characteristics. Thus, increasing attention has recently been focused on the role of immunity to non-HLA antigenic targets.

Methods: We analyzed humoral auto- and alloimmune responses to the non-HLA antigen glutathione S-transferase theta 1 (GSTT1), along with development of ()HLA-DSAs, in a cohort of 146 pediatric non-sensitized recipients of first kidney allograft, to analyze its role in ABMR and graft loss.

Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement.

CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited.

Self-Supervised Learning Across Domains.

Human adaptability relies crucially on learning and merging knowledge from both supervised and unsupervised tasks: the parents point out few important concepts, but then the children fill in the gaps on their own. This is particularly effective, because supervised learning can never be exhaustive and thus learning autonomously allows to discover invariances and regularities that help to generalize. In this paper we propose to apply a similar approach to the problem of object recognition across domains: our model learns the semantic labels in a supervised fashion, and broadens its understanding of the data by learning from self-supervised signals on the same images.

Post-transplant de novo non donor-specific HLA antibodies are not associated with poor graft outcome in non-sensitized pediatric recipients of kidney transplantation.

While de novo donor-specific HLA antibodies (dnDSAs) have a detrimental impact on kidney graft outcome, the clinical significance of de novo non donor-specific antibodies (dnNDSAs) is more controversial. We retrospectively evaluated for Ab development and characteristics of dnNDSAs serially collected post-transplant sera and, when available, graft biopsy eluates, from 144 non-sensitized, primary pediatric kidney recipients, consecutively transplanted at a single center between 2003 and 2017, using HLA class I and class II single-antigen flow-bead assays (SAB). The results were compared with clinical-pathologic data from HLA antibody negative and HLA dnDSA-positive patients.

Pretransplant Single Antigen Bead-Detected HLA Antibodies in Kidney Transplant Long-term Outcome: A Single-Center Cohort Experience.

Single-antigen bead (SAB) platform permits the identification of antibodies not detectable by complement-dependent lymphocytotoxicity test, but their clinical significance is not completely understood. The aim of this study was to evaluate whether the presence of pretransplant SAB-detected antibodies is associated with the development of allograft failure. This is a single-center cohort study with 10-year follow-up in which 573 kidney recipients with negative pretransplant complement-dependent lymphocytotoxicity crossmatch who received transplants at the Kidney Transplant Center of Policlinico, Milan, from deceased donors between 1996 and 2005 were evaluated.

Failure to remove de novo donor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss - a retrospective study.

Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment.

De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients.

De novo posttransplant donor-specific HLA-antibody (DSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for DSA occurrence by Luminex platform.

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.

Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome.

Acquisition of C3d-Binding Activity by De Novo Donor-Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients.

Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss.

Anti-Trichomonas vaginalis activity from triterpenoid derivatives.

Trichomonas vaginalis is a flagellated parasite that causes trichomonosis, the most common non-viral sexually transmitted disease (STD) in the world. Worryingly, trichomonosis is associated to increased transmission of HIV. Due to high frequency of the infection during pregnancy and the development of metronidazole-resistant isolates, therapeutic alternatives to 5-nitroimidazole are being searched.

Three-yr safety and efficacy of everolimus and low-dose cyclosporine in de novo pediatric kidney transplant patients.

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.

Synthesis of isosteric triterpenoid derivatives and antifungal activity.

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non-toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities.

In kidney transplant patients, alemtuzumab but not basiliximab/low-dose rabbit anti-thymocyte globulin induces B cell depletion and regeneration, which associates with a high incidence of de novo donor-specific anti-HLA antibody development.

In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared.

[HIV seropositive women and their partners facing the decision of a pregnancy].

The purpose of this qualitative, descriptive exploratory study is to investigate the reasons why HIV seropositive women and their partners make the decision of becoming pregnant despite the risk of vertical transmission, contamination or reinfection of the partner. The subjects of this study were six pregnant women. Data collection was done through a semi-structured questionnaire which was organized in the NVIVO 2.

Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues.

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality.

Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection.

The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti-HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical-pathologic data.

Heart transplantation with donor-specific antibodies directed toward denatured HLA-A*02:01: a case report.

The development of solid-phase assays for antibody detection has aided in the frequent detection of human leukocyte antigen (HLA) antibodies in nonalloimmunized males. Some scientists have reported that these HLA antibodies are produced to pathogens or allergens and the reactivity with HLA coated beads is the result of cross-reactive epitopes. These antibodies may also be directed toward cryptic epitopes exposed on the denatured beads.

Biochemical characterization of an ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP, E.C. 3.1.4.1) from rat cardiac soluble and microsomal fractions.

In this study, we have reported the kinetic and biochemical characterization of ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) activity in rat cardiac fractions, one soluble and the other enriched in vesicles derived from sarcoplasmic reticulum. Both fractions demonstrated E-NPP activities, which could be observed by extracellular hydrolysis of p-nitrophenyl-5'-thymidine monophosphate (p-Nph-5'-TMP) and other biochemical characteristics. The K(M) values for the hydrolysis of p-Nph-5'-TMP in soluble and microsomal fractions were 118.

Isoniazid in patient plasma may cause a false-positive result on the complement-dependent cytotoxicity test.

Correct definition of clinically relevant anti-HLA antibodies is important for transplant organ allocation and outcome. We describe a candidate for kidney transplantation who was treated with isoniazid because of active tuberculosis. The patient's serum gave a positive antibody result on screening with the complement-dependent cytotoxicity (CDC) test but a negative result on screening with a bead-based assay (Luminex).

AMP hydrolysis in soluble and microsomal rat cardiac cell fractions: kinetic characterization and molecular identification of 5'-nucleotidase.

The present study describes the enzymatic properties and molecular identification of 5'-nucleotidase in soluble and microsomal fractions from rat cardiac ventricles. Using AMP as a substrate, the results showed that the cation and the concentration required for maximal activity in the two fractions was magnesium at a final concentration of 1 mM. The pH optimum for both fractions was 9.

Luminex technology for anti-HLA antibody screening: evaluation of performance and of impact on laboratory routine.

The recent introduction of new technologies such as Luminex has provided alternative methods to the Complement Dependent Cytotoxicity (CDC) test for HLA specific antibody detection. In this study we compared the results obtained with CDC to those obtained using a Luminex method with the aim of evaluating the impact of this new technology on antibody screening policies in our transplant setting.A total of 1,421 sera, acquired from patients on the waiting list for a kidney transplant or following transplantation, were tested by both methodologies.