Transplant antibody desensitization

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...

The presence of donor-specific antibodies (DSAs) are associated with graft failure either following HLA-mismatched allogeneic stem cell transplantation or after organ transplantation. Although targeting B cells and plasma cells have been used for desensitization, there have been reports of failure. T follicular helper (Tfh) cells assist B cells in differentiating into antibody-secreting plasma cells. We used haploidentical allograft as a platform to investigate the possibility of targeting Tfh cells to desensitize DSA...

We performed a single-center retrospective cohort study of 66 consecutive ABO incompatible kidney transplants (ABOiKT) performed without B-cell depleting therapy. Outcomes were compared to an earlier era performed with rituximab ( n = 18) and a contemporaneous cohort of ABO compatible live donor transplants (ABOcKT). Acute rejection within 3 months of transplant was significantly more common after rituximab-free ABOiKT compared to ABOiKT with rituximab (OR 8.8, p = 0.04) and ABOcKT (OR 2.9, p = 0.005) in adjusted analyses...

No abstract text is available yet for this article.

Intravenous immunoglobulin (IVIG) has been developed for over 40 years. The mechanisms of action of IVIG are complex and diverse, and there may be multiple mechanisms that combine to influence it. IVIG has been used in kidney transplantation for desensitization, treatment of antibody-mediated rejection, and ABO-incompatible transplantation. and treatment or prevention of some infectious diseases. Hyperimmune globulins such as cytomegalovirus hyperimmune globulin (CMV-IG) and hepatitis B hyperimmune globulin (HBIG) have also been used to protect against cytomegalovirus and hepatitis B virus, respectively...

BACKGROUND In liver transplantation (LT), preoperative desensitization therapy is considered necessary in patients positive for donor-specific anti-human leukocyte antigen antibodies (DSAs). However, the relationship between DSA intensity and the necessary desensitization therapy is unclear. MATERIAL AND METHODS A total of 37 adult living donor (LD) LTs performed between January 2016 and March 2022 were examined. Mycophenolate mofetil (MMF) was administered preoperatively in DSA-positive cases with positive lymphocyte cross-matching who underwent LDLT...

BACKGROUND: Pretransplant therapies such as rituximab and plasmapheresis have led to an increase in ABO-incompatible (ABOi) living donor liver transplantation (LDLT), thus helping to overcome organ shortages. This study evaluated the changes in anti-A/B titers and CD19 levels over time in patients undergoing ABOi LT and aimed to understand the effect of single-nucleotide polymorphisms (SNPs) in Fc gamma receptor (FcγR) on rituximab therapy. METHODS: Two SNPs of FCGR2A (131H/R) and FCGR3A (158F/V) were identified...

Whether immunoadsorption (IADS) as part of desensitization protocols could facilitate deceased donor kidney transplantation (KT) in highly sensitized (HS) patients remains to be proven. We retrospectively analyzed our IADS based desensitization protocol for deceased donor KTs between 2013 and 2018. Fifteen HS patients (age 52 years [40-56]) were included. Waiting time before IADS was 6 years [5-10] and the interval between IADS initiation and KT was 5 months [1-12] for the 14 transplanted patients...

PURPOSE OF REVIEW: For sensitized heart transplant candidates who have antibodies to human leukocyte antigens (HLA), finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting heart transplantation has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. RECENT FINDINGS: Advances in the assessment of HLA antibodies allow for identification of heart transplant candidates who may benefit from desensitization strategies to widen the donor pool and mitigate the risk of adverse posttransplant outcomes...

PURPOSE OF REVIEW: The implementation of highly sensitive immune assays measuring anti-human leukocyte antigen (HLA) antibodies has modified alloimmune risk stratification and diagnosis of rejection. Nonetheless, anti-HLA antibodies represent the downstream effector mechanism of the B-cell response. Better characterizing the cellular components of the humoral immune response (including memory B cells (mBCs) and long-lived plasma cells) could help to further stratify the alloimmune risk stratification and enable discovery of new therapeutic targets...

No abstract text is available yet for this article.

Intensive immunosuppression has enabled liver transplantation even in recipients with preformed donor-specific antibodies (DSA), an independent risk factor for graft rejection. However, these recipients may also be at high risk of progressive multifocal encephalopathy (PML) due to the comorbid immunosuppressed status. A 58-year-old woman presented with self-limited focal-to-bilateral tonic-clonic seizures 9 months after liver transplantation. She was desensitized using rituximab and plasma exchange before transplantation and was subsequently treated with steroids, tacrolimus, and everolimus after transplantation for her preformed DSA...

BACKGROUND: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. METHODS: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. RESULTS: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21...

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case-control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control...

The presence of donor-specific antibodies (DSA), mainly against HLA, increases the risk of allograft rejection. Moreover, antibody-mediated rejection (ABMR) remains an important barrier to optimal long-term outcomes after solid organ transplantation. The development of chimeric autoantibody receptor T lymphocytes has been postulated for targeted therapy of autoimmune diseases. We aimed to develop a targeted therapy for DSA desensitization and ABMR, generating T cells with a chimeric HLA antibody receptor (CHAR) that specifically eliminates DSA-producing B cells...

UNLABELLED: Incompatible living donor kidney transplant recipients (ILDKTr) require desensitization to facilitate transplantation, and this substantial upfront immunosuppression may result in serious complications, including cancer. METHODS: To characterize cancer risk in ILDKTr, we evaluated 858 ILDKTr and 12 239 compatible living donor kidney transplant recipients (CLDKTr) from a multicenter cohort with linkage to the US transplant registry and 33 cancer registries (1997-2016)...

BACKGROUND: Renal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization. METHODS: Fifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included...

In cases of acute liver failure (ALF) with hepatic coma, early liver transplantation, including ABO-incompatible (ABOi) living donor liver transplantation (LDLT), should be considered. The ABO antibody barrier can be reduced using plasma exchange (PE) and the anti-CD20 antibody rituximab. Plasma exchange is also performed for drug-induced ALF and is effective for desensitization. Rituximab treatment usually requires 14 days. There is presently no established desensitization protocol for ABOi-LDLT for ALF...

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection...