Development of Non-ABO Red Blood Cell Alloantibodies in Patient Undergoing Allogeneic Haematopoietic Stem Cell Transplant

Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.

Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells in the complex milieu of the liver.In this section,we will comment on the importance of donorspecific anti-human leukocyte antigen(HLA)antibodies(DSA)as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor(KIR)genotypes in the evolution of liver transplantation.Thus,HLA compatibility,viral infections,and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival.There have been reports of increased risk of acute and chronic rejection with ductopenia,faster graft fibrosis,biliary problems,poorer survival,and even de novo autoimmune hepatitis when DSAs are present in the recipient.Higher mean fluorescence intensity(MFI)values of the DSAs and smaller graft size were associated with poorer patient outcomes,implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods,according to the investigators.Similarly,in a combined kidney-liver transplant,a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment.The renal graft was lost owing to antibody-mediated rejection(AMR).The HLA antigens expressed by the transplanted liver graft influenced antibody elimination.Pathologists are increasingly diagnosing AMR in liver transplants,and desensitization therapy has even been employed in situations of AMR,particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex.In conclusion,after revealing the negative impacts of DSAs with high MFI,pretransplant virtual crossmatch techniques may be appropriate to improve evolution;however,they may extend cold ischemia periods by requiring the donor to be typed.

Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies

BACKGROUND Erythrocyte alloantibodies are mainly produced after immune stimulation,such as blood transfusion,pregnancy,and transplantation,and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching.Therefore,antibody screening is critical to prevent and improve red cell alloantibodies.Routine tube assay is the primary detection method of antibody screening.Recently,erythrocyte-magnetized technology(EMT)has been increasingly used in clinical practice.This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion.AIM To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice.METHODS A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022.A 5 mL blood sample was collected in tubing,which was then cut,and the whole blood was put into a test tube for centrifugation to separate the serum.Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test,tube antiglobulin test(AGT),and EMT screening irregular antibody methods to determine the best test method.RESULTS Simultaneous detection was performed through the tube polybrene test,tube AGT and EMT screening irregular antibodies.It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G(IgG)and immunoglobulin M(IgM)irregular antibodies,and the results of manual tube AGT were satisfactory,but the operation time was lengthy,and the equipment had a large footprint.The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh(D)red blood cells,and the outcomes were satisfactory.Furthermore,compared to the conventional tube method,the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency.CONCLUSION With a higher detection rate,the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.

HLA and lung transplantation

Lung transplantation is increasingly practiced for patients with end-stage lung disease.The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies,mainly directed against the protein products of the HLA complex of the organ donor.While the association between antibody mediated rejection and ailograft damage has been well established in renal and heart transplantation,it has not yet been well characterized in lung transplantation.This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class Ⅰ and Ⅱ antigens.The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo posttransplant circulating antibodies.Finally,potential mechanisms,which may act individually or in combination,of antibody mediated damage to solid organ transplants are considered.

Antibodies against major histocompatibility complex class I-related chain A in transplant recipients

Objective To review the role of polymorphism of major histocompatibility complex class I-related chain A （MICA） gene and antibodies against MICA antigens in transplant immunology. Data sources The data used in this review were mainly from our own results and from the relevant English language literatures published from 1999 to 2010. Some data presented in this review are in press.Study selection Articles regarding MICA gene discovery and pioneering finding of antibodies against MICA antigen and allograft rejection were selected. This review chronicles the development of our understanding of the role that MICA antigens and antibodies may play in organ transplantation.Results Polymorphic glycoprotein MICA antigens were detected on freshly isolated human umbilical cord endothelial cells, but not on peripheral lymphocytes. Antibodies were found and typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. The specificity of antibodies against the epitopes of MICA antigens were well characterized by donor MICA typing, single antigen array testing with antibody absorption and elution. Acute graft-versus-host disease was observed in stem-cell recipients who were mismatched for MICA.Conclusions Immunization against mismatched MICA epitopes encountered in donor organs after transplantation may result in antibodies against MICA alleles. Testing for MICA donor-specific antibodies （DSA） which are associated with early failure of kidney transplants may be helpful for identifying some of the targets of antibodies against antigens other than the human leukocyte antigen （HLA） and for improving transplantation outcome.

Role of proteasome inhibition in sensitized transplant candidates

Objective To review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate. Data sources The data used in this review were from articles published （PubMed） between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used. Study selection Articles were selected if they were trial results or case studies for the use of bortezomib in the sensitized patient population.Results The early data using bortezomib as a part of desensitization regimens has shown success. Although one cycle （4 doses） of bortezomib seems to have affect on many patients, it also seems likely that to provide complete desensitization multiple cycles will be required. Regarding safety, bortezomib has been shown to have minimal side effects. The most common side effects reported are those of thrombocytopenia and anemia. These side effects are dose related and self limiting upon discontinuation of the treatment.Conclusions Bortezomib with plasmapheresis is a promising new alternative to desensitization protocols that use either high dose intravenous immune globulin （IVIG） or low dose IVIG and plasmapheresis. The efficacy on antibody reduction looks to be batter that that of the IVIG based regimens without significant addition toxicity. The results of ongoing prospective trials are positive and their complete results are greatly anticipated.