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Cureus May 2024This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a... (Review)
Review
This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a significant medical issue that can cause haemolytic disease of the fetus and newborn (HDFN), leading to neonatal morbidity and mortality. Current HDFN prophylaxis targets only Rhesus D (RhD) alloimmunization, with no effective measures to prevent alloimmunization to other RBC antigen groups. Several factors can increase the risk of developing RBC alloimmunization during pregnancy, including fetomaternal haemorrhage, RBC and maternal genetic status, and previous transfusions. Identifying these risk factors is essential to execute the appropriate management strategies to minimize the risk of HDFN. The review also discusses the laboratory methods and overview of pregnancy management. The paper highlights the importance of identifying and managing the risk factors for RBC alloimmunization in pregnancy to minimize the risk of HDFN and improve neonatal outcomes.
PubMed: 38868295
DOI: 10.7759/cureus.60158 -
Transfusion Medicine and Hemotherapy :... Jun 2024Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the...
INTRODUCTION
Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8 T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo.
METHODS
PIRCHE-I analysis was performed to identify HLA-DPB1-derived peptides that could theoretically bind to HLA-A*02:01. PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro by investigating binding affinities of HLA-DPB1-derived peptides to the HLA-A*02:01 in a competition-based binding assay. To investigate the capacity of HLA-DPB1-derived peptides to elicit a T-cell response in vivo, mice were immunized with these peptides. T-cell alloreactivity was subsequently evaluated using an interferon-gamma ELISpot assay.
RESULTS
The PIRCHE-I algorithm identified five HLA-DPB1-derived peptides (RMCRHNYEL, YIYNREEFV, YIYNREELV, YIYNREEYA, and YIYNRQEYA) to be presented by HLA-A*02:01. Binding of these peptides to HLA-A*02:01 was confirmed in a competition-based peptide binding assay, all showing an IC value of 21 μm or lower. The peptides elicited an interferon-gamma response in vivo.
CONCLUSION
Our results indicate that the PIRCHE-I algorithm can identify potential immunogenic HLA-DPB1-derived peptides present in recipients of an HLA-DPB1-mismatched donor. These combined in vitro and in vivo observations strengthen the validity of the PIRCHE-I algorithm to identify HLA-DPB1 mismatch-related GvHD development upon HSCT.
PubMed: 38867810
DOI: 10.1159/000537789 -
Journal of Pediatric Hematology/oncology Jul 2024Sickle cell disease (SCD) is a common hereditary hemoglobin disorder worldwide. One of the main treatments for patients with SCD is the requirement for blood...
OBJECTIVE
Sickle cell disease (SCD) is a common hereditary hemoglobin disorder worldwide. One of the main treatments for patients with SCD is the requirement for blood transfusions. Posttransfusion alloimmunization with red blood cell (RBC) antigens continues to be a major risk factor for SCD. The objective of this study was to determine the rate, nature, and risk factors of red cell alloimmunization among pediatric patients with SCD in our center and compare our results with published reports from Saudia Arabia SA, regional countries, and some international countries.
MATERIALS AND METHODS
A retrospective chart review of patients with SCD at King Abdulaziz Medical City-Jeddah, between 2008 and 2019 was performed. Demographic characteristics and transfusion histories were recorded. Blood samples were analyzed for alloimmunization using immunohematologic techniques.
RESULTS
In total, 121 patients were analyzed. Alloantibodies were detected in 21 patients (17.4%) and were mostly single in 15 patients (71.4%), anti-K (23.7%), anti-E (19.0%), and anti-S (9.5%). The other 6 patients (28.6%) had multiple alloantibodies, especially the combination of anti-C and anti-K (9.5%) and the combination of anti-C and anti-E (9.5%). Alloantibody levels were significantly higher in patients with frequent hospital admissions (>5 times annually), those who had an exchange blood transfusion, those younger than 3 years old, and those who received a larger number of blood units ( P ≤0.05).
CONCLUSION
The rate of RBC alloimmunization is determined and considered relatively low compared with that in other nations. Matching for extended RBC antigens to include ABO, RH (D, C, c, E, e), K, Fy a , Fy b , Jk a , and Jk b antigens in the screening panel for donors and recipients is highly recommended to ensure better transfusion practices and avoid transfusion-related complications.
Topics: Humans; Anemia, Sickle Cell; Saudi Arabia; Child; Male; Retrospective Studies; Female; Isoantibodies; Child, Preschool; Adolescent; Prevalence; Erythrocytes; Infant; Blood Group Incompatibility; Blood Group Antigens; Risk Factors; Blood Transfusion
PubMed: 38857199
DOI: 10.1097/MPH.0000000000002889 -
Case Reports in Women's Health Jun 2024Fetal hemolysis is caused by maternal antibodies that cross the placenta. Anti-M antibodies can rarely cause severe forms of alloimmunization in the fetus and newborn....
Fetal hemolysis is caused by maternal antibodies that cross the placenta. Anti-M antibodies can rarely cause severe forms of alloimmunization in the fetus and newborn. We present a case of severe anti-M alloimmunization requiring a total of 8 intrauterine transfusions, in a patient with a prior poor obstetrical history. A 35-year-old Iranian pregnant woman with a prior obstetrical history of one abortion and two stillbirths was found to have had anti-M antibody titers 1:8 and accompanying elevated middle cerebral artery peak systolic velocity (MCA-PSV) of 1.9 MoM suggestive of severe fetal anemia at 17 weeks of gestation. Persistently elevated fetal MCA-PSV was noted despite intraperitoneal transfusion at 17, 19, and 22 weeks. Fetal blood sampling at 27 weeks confirmed severe fetal anemia (3 g/dL), which required additional intravascular and intraperitoneal blood transfusion. At 37 weeks, elective cesarean section was performed. Neonatal hemoglobin immediately after delivery was 10.1 g/dL. In addition to standard supportive care, the neonate required two additional transfusions and remained in the neonatal intensive care unit (NICU) for 23 days. Anti-M antibodies are a rare cause of severe alloimmunization. We present a case in order to improve management.
PubMed: 38855719
DOI: 10.1016/j.crwh.2024.e00620 -
The Journal of Clinical Investigation Jun 2024Although antibody-mediated lung damage is a major factor in transfusion-related acute lung injury (ALI), autoimmune lung disease (for example, coatomer subunit α [COPA]...
Although antibody-mediated lung damage is a major factor in transfusion-related acute lung injury (ALI), autoimmune lung disease (for example, coatomer subunit α [COPA] syndrome), and primary graft dysfunction following lung transplantation, the mechanism by which antigen-antibody complexes activate complement to induce lung damage remains unclear. In this issue of the JCI, Cleary and colleagues utilized several approaches to demonstrate that IgG forms hexamers with MHC class I alloantibodies. This hexamerization served as a key pathophysiological mechanism in alloimmune lung injury models and was mediated through the classical pathway of complement activation. Additionally, the authors provided avenues for exploring therapeutics for this currently hard-to-treat clinical entity that has several etiologies but a potentially focused mechanism.
Topics: Humans; Immunoglobulin G; Acute Lung Injury; Complement Activation; Animals; Isoantibodies; Protein Multimerization; Histocompatibility Antigens Class I; Antigen-Antibody Complex
PubMed: 38828725
DOI: 10.1172/JCI181137 -
Clinical Hematology International 2024Hematopoietic stem cell transplantation (HSCT) is a cornerstone of modern medical practice, and can only be performed safely and effectively with appropriate transfusion... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) is a cornerstone of modern medical practice, and can only be performed safely and effectively with appropriate transfusion medicine support. Patients undergoing HSCT often develop therapy-related cytopenia, necessitating differing blood product requirements in the pre-, peri-, and post-transplant periods. Moreover, ensuring optimal management for patients alloimmunized to human leukocyte antigens (HLA) and/or red blood cell (RBC) antigens, as well as for patients receiving ABO-incompatible transplants, requires close collaboration with transfusion medicine and blood bank professionals. Finally, as updated transfusion guidelines and novel blood product modifications emerge, the options available to the transplant practitioner continue to expand. Herein, we detail contemporary blood transfusion and transfusion medicine practices for patients undergoing HSCT.
PubMed: 38817704
DOI: 10.46989/001c.94135 -
Frontiers in Immunology 2024Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA)....
Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11bCD11c), mature (CD11bCD11cMHCII) and active (CD11bCD11cCD40) DCs and cDC2 subset (CD11bCD11c MHCII) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4IL-17) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.
Topics: Animals; Dendritic Cells; Skin Transplantation; Mice; Hindlimb; Graft Rejection; Mice, Inbred C57BL; Mice, Inbred BALB C; Composite Tissue Allografts; Vascularized Composite Allotransplantation; CD8-Positive T-Lymphocytes; Male; Tissue Donors; Skin
PubMed: 38799435
DOI: 10.3389/fimmu.2024.1395945 -
Biomedical Journal May 2024After transplantation of allogeneic tissues and organs, recognition by recipient T cells of donor MHC molecules initiates the pro-inflammatory adaptive immune response...
After transplantation of allogeneic tissues and organs, recognition by recipient T cells of donor MHC molecules initiates the pro-inflammatory adaptive immune response leading to allograft rejection. T cell allorecognition has long been known to be mediated via two distinct pathways: the direct pathway in which T cells recognize intact allogeneic MHC molecules displayed on donor cells and the indirect pathway whereby T cells recognize donor MHC peptides processed and presented by recipient antigen-presenting cells (APCs). It is believed that direct allorecognition is the driving force behind early acute allograft rejection while indirect allorecognition is involved in chronic allograft rejection, a progressive condition characterized by graft vasculopathy and tissue fibrosis. Recently, we and others have reported that after transplantation of allogeneic skin and organs, donor MHC molecules are transferred from donor cells to the host's APCs via trogocytosis or extracellular vesicles. Recipient APCs having captured donor MHC molecules can either present them to T cells in the intact form on their surface (semi-direct pathway) or the form of peptides bound to self-MHC molecules (indirect pathway). The present article provides an overview of recent studies evaluating the role of intercellular exchange of MHC molecules in T cell alloimmunity and its contribution to allograft rejection and tolerance.
PubMed: 38797478
DOI: 10.1016/j.bj.2024.100749