Transplant antibody desensitization

BACKGROUND: In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. METHODS: It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period...

In patients requiring haploidentical hematopoietic cell transplant (haplo-HCT), the presence of donor specific anti-HLA antibodies (DSAs) is associated with high rates of primary graft failure and poor overall survival (OS). There is limited data regarding the effect of desensitization. Adult patients undergoing haplo-HCT at Washington University School of Medicine from 2009- 2021 were identified. Patients were divided into three cohorts: no DSA, untreated DSA or treated DSA. DSA testing was performed. Desensitization therapy using plasmapheresis and IVIg (immunoglobulin) was performed...

Heart transplantation (HTx) is the only definitive therapy for patients with end stage heart disease. With the increasing global prevalence of heart failure, the demand for HTx has continued to grow and outpace supply. In this paper, we will review advances in the field of HTx along the clinical journey of a HTx recipient. Starting with the sensitized patient, we discuss current methods to define sensitization, and assays to help identify clinically relevant anti-HLA antibodies. Desensitization strategies targeting all levels of the adaptive immune system are discussed with emphasis on novel techniques such as anti-CD 38 blockade and use of the Immunoglobulin G-Degrading Enzyme of Streptococcus Pyogenes...

Neutralizing capacity measurement (NCM) of soluble ABH substances (SAS) in plasma was assessed to guide the selection of the appropriate ABO group of fresh-frozen plasma (FFP) for plasma exchange (PE) in blood group O recipients with ABO-incompatible transplantations. Neutralizing capacity was assessed by measuring anti-A and/or anti-B titers in samples comprising one unit of O FFP and 10 O EDTA plasma samples and subtracting the binary logarithm of the titer in each group with a saline dilution. Ten EDTA plasma samples with Lewis b (Leb ) antigen positivity and 10 sets of pooled FFP from each blood group were used as diluents...

Liver transplantation (LT) is the only life-saving option when acute-on-chronic liver failure (ACLF) does not improve with conservative therapy. Acute pancreatitis (AP) can cause chronic liver disease progression to ACLF. However, deceased donor LT for patients with AP has had mixed results, and no consensus has been established regarding the indication for LT. We report the first successful living donor LT (LDLT) for ACLF caused by severe AP. The 38-year-old patient with alcoholic liver disease was transferred to our institute with worsening refractory ascites...

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BACKGROUND: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments. We investigated the medical costs of high-immunological-risk kidney transplantation in comparison with the cost of hemodialysis in Japan...

SIGNIFICANCE STATEMENT: There is no standardized desensitization regimen for kidney transplant candidates. CD38, expressed by plasma cells, could be targeted for desensitization to deplete plasma cells producing alloantibodies and donor-specific antibodies. Few studies and case reports are available regarding the use of CD38 antibodies for desensitization in patients awaiting kidney transplant. This study shows that isatuximab, a CD38-targeting therapy, was well tolerated in kidney transplant candidates, with a durable decrease in anti-HLA antibodies and partial desensitization activity...

Anesthesiologists should be aware of the coagulation implications of therapeutic plasma exchange (TPE) with albumin replacement for desensitization of kidney transplant (KT) recipients. We describe a case where the final preoperative TPE was performed with albumin. A TEGR 6s demonstrated defects in fibrinogen component to clot strength. With surgical oozing noted and the fibrinogen defect, cryoprecipitate was administered. Thereafter, fibrinogen contribution to clot strength normalized, coinciding with clinical hemostasis...

Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs). We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation. We find that treatment of allo-sensitized hosts with CAR T cells targeting Bmems and LLPCs eliminates donor-specific allo-antibodies (DSAs) and mitigates hyperacute rejection of subsequent islet allografts...

BACKGROUND The management and fate of liver transplant (LT) recipients with preformed donor-specific antibodies (pDSA) remain controversial. The aim of this study was to evaluate the clinical impact of rituximab desensitization on pDSA in LT recipients. MATERIAL AND METHODS This retrospective observational study enrolled 120 LT patients aged ≥18 years. Patients with pDSA were administered 500 mg/body rituximab 1-21 days before LT, except for those who had an active infection or had insufficient time to receive rituximab...

PURPOSE OF REVIEW: Human leukocyte antigen (HLA) sensitization is a major barrier to kidney transplantation induced by exposure to alloantigens through pregnancy, blood product exposure and previous transplantations. Desensitization strategies are undertaken to improve the chances of finding compatible organ offers. Standard approaches to desensitization include the use of plasmapheresis/low dose intravenous immunoglobulin (IVIG) or high dose IVIG plus anti-CD20. However, current methods to reduce HLA antibodies are not always successful, especially in those with calculated panel reactive antibody 99-100%...

BACKGROUND: With the improvement of immunosuppressive regimens, the success rate and availability of ABO-incompatible (ABO-i) kidney transplantation (KT) have gradually increased. However, the management of immunosuppression protocols and complications associated with ABO-i KT is complex. Here, we report a clinical case of ABO-i living donor KT with allograft dysfunction caused by acute blood group antibody-dependent rejection triggered by human parvovirus B19 (B19V). CASE REPORT: The ABO blood group of the recipient was O, and that of the donor was B...

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation...

This study investigates the influence of donor-specific anti-HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo-SCT) with rituximab desensitization. A total of 155 DSA-positive haplo-SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high-risk patients...

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation...

To explore the desensitization treatment of patients waiting for kidney transplantation, this article comparative analysis of the effect of splenic irradiation on mean fluorescence intensity (MFI) values of HLA antibodies of 4 presensitized patients. After splenic irradiation, the mean MFI values of HLA-I antibody in 4 patients all decreased (P ≤ .001, P ≤ .001, P ≤ .001, P ≤ .001), and 3 patients had a decrease in intensity level (P ≤ .001, P = .001, P ≤ ...

BACKGROUND: Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor-specific antibody (DSA), albeit with rebound. METHODS: IdeS was generated and tested (2 mg/kg, IV) in two naïve and four allosensitized nonhuman primates (NHP)...

BACKGROUND: In the setting of mismatched-hematopoietic stem cells transplantation, the detection of antibodies directed against donor-specific HLA allele(s) or antigen(s) (DSA) represents a barrier for engraftment. It is thus necessary to plan an immunosuppressive strategy, or to select an alternative donor. This prospective study aimed at evaluating the efficacy of our strategy for testing DSAs and the efficacy of the desensitization strategy (DS) employed between November 2017 and November 2020...

BACKGROUND: The use of bortezomib which is a proteasome inhibitor has been demonstrated to be efficacious in small number of patients as a desensitization strategy in heart transplant. We reviewed our single center's experience using Bortezomib along with plasmapheresis as desensitization therapy for highly sensitized patients to assess pre- and post-transplant outcomes. METHOD: We assessed 43 highly sensitized patients awaiting HTx (defined as cPRA > 50%) between 2010 and 2021 who underwent desensitization therapy with bortezomib...