allo antibodies

Antibody-mediated rejection (AMR) can cause graft failure following renal transplantation. Neutrophils play a key role in AMR progression, but the exact mechanism remains unclear. We investigated the effect of neutrophils on AMR in a mouse kidney transplantation model. The mice were divided into five groups: syngeneic transplantation (Syn), allograft transplantation (Allo), and three differently treated AMR groups. The AMR mouse model was established using skin grafts to pre-sensitize recipient mice. Based on the AMR model, Ly6G-specific monoclonal antibodies were administered to deplete neutrophils (NEUT-/- + AMR) and TACI-Fc was used to block B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) signaling (TACI-Fc + AMR)...

BACKGROUND: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. METHODS: This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022...

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: Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL. METHODS: A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed...

Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR-T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative...

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression...

OBJECTIVE: This paper observes the efficacy of chemotherapy combined with CD19 and CD20 monoclonal antibodies in clearing minimal residual disease (MRD) and bridging transplantation for refractory acute B-lymphoblastic leukemia (B-ALL) in children and reviews the literature. METHODS: A 4-year-old boy diagnosed with B-ALL in our hospital was treated with the SCCLG-ALL-2016 protocol. MRD and gene quantification decreased after induction but remained persistently positive, with poor efficacy...

Objective: To explore the feasibility of sirolimus as an alternative graft versus host disease (GVHD) prophylaxis in patients with kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective case series study. Medical records of 11 patients in Peking University People's Hospital from 1 August 2008 to 31 October 2022, who received sirolimus instead of cyclosporine to prevent GVHD, due to renal insufficiency after allo-HSCT, were analyzed retrospectively. Incidence of GVHD, infection, and transplant-associated thrombotic microangiopathy (TA-TMA), as well as renal function, were evaluated...

Few studies have performed comparative analysis of the outcome of hematopoietic stem cell transplantation from HLA-identical sibling donors (ISD-HSCT) in patients with or without anti-HLA Abs. In this study we retrospectively collected data from a multicenter study to analyze the distribution and impact of the pre-existing anti-HLA Abs in ISD-HSCT. Among 402 recipients, 111 were positive for anti-HLA Abs. Gender, time from diagnosis to transplantation and distribution of primary disease might be risk factors for the occurrence of anti-HLA Abs...

BACKGROUND: Chronic graft-versus-host disease (cGvHD) is a major complication that puts patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at risk of death or infection. Currently, there is no gold standard for the first-line treatment of patients who do not respond to steroids, and there are several therapeutic options being evaluated in clinical trials for this disease to be used even in the first-line treatment for GvHD. There is evidence of the benefit of rituximab, an anti-CD20 antibody, at a standard dose of 375 mg/m2 weekly in the treatment of steroid-refractory chronic graft-versus disease (SR-cGvHD)...

BACKGROUND: Antibodies against human neutrophil antigen (HNA) are involved in the pathogenesis of neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion-related acute lung injury. The present methods for anti-HNA antibody identification strongly depend on the presence of standard antisera with known allo/isospecificities. Here, we aimed to produce recombinant humanized antibodies to HNA from available mouse monoclonal antibodies (MoAbs). STUDY DESIGN AND METHODS: RNAs were extracted from available hybridoma cells producing mouse anti-HNA antibodies recognizing HNA-1a (TAG-1), -1b (TAG-2), -2 (TAG-4), and FcγRIIIb, and the cDNA was synthesized...

Allogeneic transplant organs are potentially highly immunogeneic. The endothelial cells (EC) located within the vascular system serve as the primary interface between the recipient's immune system and the donor organ, playing a key role in the allo-immune response. In this study, we investigated the potential use of recipient-derived ECs in a vein recellularization model. Here, human iliac veins underwent complete decellularization using a triton X-100 protocol. We demonstrated the feasibility of re-endothelializing acellular blood vessels using either HUVEC or human venous-derived ECs, with this re-endothelization being sustainable for up to 28 days in vitro...

Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL...

Antibody-mediated rejection (AMR) is a risk factor for chronic lung allograft dysfunction, which impedes long-term survival after lung transplantation. There are no reports evaluating the efficacy of the single use of anti-CD20 antibodies (aCD20s) in addition to calcineurin inhibitors in preventing AMR. Thus, this study aimed to evaluate the efficacy of aCD20 treatment in a murine orthotopic lung transplantation model. Murine left lung transplantation was performed using a major alloantigen strain mismatch model (BALBc (H-2d) → C57BL/6 (BL/6) (H-2b))...

This prospective observational study aimed to assess the serological response and safety after the third booster shot of SARS-CoV-2 mRNA vaccines in 292 hematopoietic cell transplant (HCT) recipients. In our patients, mild systemic reactions were present in 10-40% and GVHD aggravation in 1.1%. Overall, clinically relevant response (>250 U/mL) was observed in 93.1% of allogeneic (allo)-HCT recipients and 70.6% of autologous (auto)-HCT recipients, respectively. Of note, detectable antibody response with any titer following the first two doses was a powerful predictor for adequate response after booster shot in both cohorts...

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: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell therapy (CART) recipients who develop COVID-19 can have decreased overall survival, likely due to disease-inherent and therapy-related immunodeficiency. The availability of COVID-19 directed therapies and vaccines have improved COVID-19 related outcomes, but immunocompromised individuals remain vulnerable. Specifically, the effects of SARS-CoV-2 variant infections, including Omicron and its sublineages, particularly in transplant recipients, are yet to be defined...

BACKGROUND AND OBJECTIVES: In Japan, the prevalence of haptoglobin deficiency is approximately 1 in 4000. Haptoglobin-deficient individuals may produce anti-haptoglobin from allo-immunization, leading to serious transfusion reactions. Therefore, implementation of a consistent supply of haptoglobin-deficient fresh frozen plasma is crucial. We developed a novel reagent to facilitate large-scale identification of haptoglobin-deficient individuals as potential donors of plasma products. MATERIALS AND METHODS: We established mouse monoclonal anti-haptoglobin-producing cell lines (three clones) using the hybridoma method by immunizing mice with the haptoglobin protein...

The Rhesus (Rh) blood group is a significant and complicated biological system in humans. Incompatible transfusion or pregnancy with Rh antigens can lead to the production of alloantibodies, among which the anti-E antibody is prevalent. The relationship between Anti-E antibody and HLA-II gene polymorphism in Chinese pregnant women is worth exploring. Our aim in this study was to verify the correlation between HLA-II gene polymorphisms and RhE alloimmunization in pregnant Chinese women through HLA-II typing and DR-RhE structural prediction...

Medium-dose etoposide (ETP), cyclophosphamide (CY) and total body irradiation (TBI) is a beneficial conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in adults with acute lymphoblastic leukemia (ALL), especially with high-risk ALL, as compared with CY and TBI conditioning. ETP may enhance immunogenicity of leukemia-associated antigens through increased expression of major histocompatibility antigen complex class I, leading to cross-priming of T cells by dendritic cells and generating leukemia-specific cytotoxic T cells...