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American Journal of Transplantation :... Oct 2020The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and... (Review)
Review
The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design.
Topics: Graft Rejection; Group Processes; HLA Antigens; Histocompatibility; Isoantibodies; Kidney Transplantation
PubMed: 32342639
DOI: 10.1111/ajt.15937 -
Anemia 2023The risk of developing transfusion-related complications, especially alloimmunization, is an ongoing concern for transfusion-dependent patients. It is important to...
INTRODUCTION
The risk of developing transfusion-related complications, especially alloimmunization, is an ongoing concern for transfusion-dependent patients. It is important to determine the rate of alloimmunization and autoimmunization in Al-Ahsa Region, Saudi Arabia, where sickle cell disease (SCD) and thalassemia incidence rates are the highest in Saudi Arabia.
METHODS
A cross-sectional study was conducted to review the transfusion history of patients with SCD and thalassemia at the King Fahad Hospital (KFH) in Al-Ahsa, Saudi Arabia. 364 transfusion-dependent patients were included in this study.
RESULTS
Alloimmunization rates in patients with SCD and thalassemia were 16.7% and 11.97%, respectively, while autoimmunization rates in patients with SCD and thalassemia were 5.3% and 0.7%, respectively. The most frequent alloantibodies among the study participants were against Kell, Rh blood group systems.
CONCLUSION
Blood transfusion-related alloimmunization and autoimmunization compromise the proper management of chronically transfused patients. Ideally, extended matched phenotyping should be implemented to prevent alloimmunization and reduce the risk of developing blood transfusion-related alloantibodies.
PubMed: 37152479
DOI: 10.1155/2023/3239960 -
Mediterranean Journal of Hematology and... 2022Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD) but pose significant clinical challenges. We aim to assess infectious...
CONTEXT AND OBJECTIVES
Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD) but pose significant clinical challenges. We aim to assess infectious markers, red cell alloimmunization, and iron overload secondary to BT in SCD patients.
MATERIALS AND METHODS
This case-control study included 253 SCD (153 SCD-transfused and 100 SCD non-transfused). We evaluated the transfusion practice (modalities, indications), post-transfusion complications (infections, alloimmunization, iron overload), and risk factors of these complications (socio-demographic, clinical, biological).
RESULTS
Median age was 28.5 years (5 - 59). The sex ratio was 0.86. Homozygous SCD was the most common (95.3%). Simple BT was performed in 92.8% and transfusion exchange in 18.9%. Transfusion indications were dominated by acute anemia (57.06%) and vaso-occlusive crisis (VOCs) (14%). Red blood cell concentrates (RBCSs) were administered to 93.46%. The median RBCs received per patient was 10 (2 - 48). The prevalence of VHC in SCD-transfused was 1.33% and 2% for VHB. Anti-HIV antibodies were not found. Red cell alloimmunization frequency was 16%. The most common alloantibodies were anti-rhesus (34.19%) and anti-Kell (23.67%). Iron overload was detected in 7.84%. The number of RBCs transfused was the only risk factor for alloimmunization (p = 0.03) and iron overload (p = 0.023). BT frequency was not related to infectious transmission.
CONCLUSION
BT therapy is still a risk for SCD polytransfused patients despite advances in blood safety. Although infectious transmission has rare, the risk of alloimmunization and iron overload is high in these patients.
PubMed: 35070211
DOI: 10.4084/MJHID.2022.004 -
Frontiers in Immunology 2024
Topics: Histocompatibility; Transplantation Immunology
PubMed: 38558808
DOI: 10.3389/fimmu.2024.1393026 -
Transfusion and Apheresis Science :... Feb 2020Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is the platelet counterpart of haemolytic disease of the foetus and newborn. Among Caucasians, around 80 % of... (Review)
Review
Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is the platelet counterpart of haemolytic disease of the foetus and newborn. Among Caucasians, around 80 % of FNAIT cases and some of the most severe cases, are caused by alloantibodies against the human platelet antigen 1a (HPA-1a). For around 3 decades it has been known that almost all HPA-1a-immunised women are HLA-DRB3*01:01 positive. The HLA molecule encoded by the HLA-DRA/DRB3*01:01 genes seems to be of crucial importance for initiating the immune response against HPA-1a. The HLA-DRB3*01:01 carrier status is not only important as a risk factor for immunisation, but does also have a significant impact on foetal/neonatal outcome. The possible role of HLA-DRB3*01:01 typing as tool for risk stratification is discussed.
Topics: Alleles; Antigens, Human Platelet; Fetus; HLA-DRB3 Chains; Humans; Integrin beta3; Isoantibodies; Thrombocytopenia, Neonatal Alloimmune
PubMed: 31919011
DOI: 10.1016/j.transci.2019.102707 -
Alternative Therapies in Health and... Sep 2023Neonatal alloimmune thrombocytopenia (NAIT) is an immune disorder characterized by maternal antibodies that destroy fetal platelets, leading to thrombocytopenia. The... (Review)
Review
BACKGROUND
Neonatal alloimmune thrombocytopenia (NAIT) is an immune disorder characterized by maternal antibodies that destroy fetal platelets, leading to thrombocytopenia. The prevalence of NAIT is approximately 0.05% to 0.15%. Fetal and neonatal severe thrombocytopenia represents the most common form of the disease, primarily occurring in firstborn children. It poses a greater risk and harm to the fetus and newborn. Neonatal intracranial hemorrhage is a severe complication of NAIT, resulting in irreversible damage to cranial nerves and potential neonatal death.
OBJECTIVE
This study aims to assess the current advancements in the pathogenesis, clinical characteristics, laboratory evaluation, and therapeutic interventions for neonatal alloimmune thrombocytopenia.
METHODS
This narrative review explores neonatal alloimmune thrombocytopenia through a thorough literature review. The study encompasses the pathogenesis, clinical features, laboratory examination, and treatment options associated with this condition.
RESULTS
The results of this study highlight that despite the extremely low incidence of NAIT, it carries a high risk. Currently, there is no timely and effective prevention method available. However, using HPA-1a as a screening item for prenatal prevention shows the potential to reduce the mortality rate of NAIT fetuses. Further research is required to evaluate its accuracy and specificity.
CONCLUSIONS
The findings of this review emphasize the need for further research to develop effective prevention methods. The use of HPA-1a as a screening tool holds promise but requires additional investigation. Enhancing clinical understanding of NAIT will contribute to improved management and outcomes for affected infants.
Topics: Child; Infant; Infant, Newborn; Female; Pregnancy; Humans; Thrombocytopenia, Neonatal Alloimmune; Blood Platelets
PubMed: 37318890
DOI: No ID Found -
Transfusion and Apheresis Science :... Feb 2020Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.
Topics: Humans; Infant, Newborn; Thrombocytopenia, Neonatal Alloimmune
PubMed: 31974030
DOI: 10.1016/j.transci.2019.102704 -
American Journal of Transplantation :... Apr 2016De novo induction of organized lymphoid aggregates at nonlymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as... (Review)
Review
De novo induction of organized lymphoid aggregates at nonlymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as infectious agents, autoantigens or alloantigens, persist. The prevailing opinion in the field of transplantation is that lymphoid neogenesis within allografts is detrimental to the establishment of immune tolerance. These structures, commonly referred to as tertiary lymphoid organs (TLOs), are thought to contribute to graft rejection by generating and propagating local alloimmune responses. However, recent studies have shown that TLOs rich in regulatory Foxp3(+) cells are present in long-term accepting allografts. The notion that TLOs can contribute to the local downregulation of immune responses has been corroborated in other chronic inflammation models. These findings suggest that contrary to previous suggestions that the induction of TLOs in allografts is necessarily harmful, the induction of "tolerogenic" TLOs may prove advantageous. In this review, we discuss our current understanding of how TLOs are induced and how they regulate immune responses with a particular focus on alloimmunity.
Topics: Allografts; Animals; Graft Rejection; Humans; Immune Tolerance; Lymphoid Tissue; Organ Transplantation
PubMed: 26614734
DOI: 10.1111/ajt.13645 -
Transplantation Nov 2017Whether a transplanted allograft is stably accepted, rejected, or achieves immunological tolerance is dependent on the frequency and function of alloreactive... (Review)
Review
Whether a transplanted allograft is stably accepted, rejected, or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft. In the clinic, identification and quantification of graft-reactive T and B cells allows for the early diagnosis of immune reactivity and therapeutic intervention to prevent graft loss. In addition to rejection, probing of T and B cell fate in vivo provides insights into the underlying mechanisms of alloimmunity or tolerance that may lead to biomarkers predicting graft fate. In this review, we discuss existing and developing approaches to track and analyze alloreactive T and B cells in mice and humans and provide examples of discoveries made utilizing these techniques. These approaches include mixed lymphocyte reactions, trans-vivo delayed-type hypersensitivity, enzyme-linked immunospot assays, the use of antigen receptor transgenic lymphocytes, and utilization of peptide-major histocompatibility multimers, along with imaging techniques for static multiparameter analysis or dynamic in vivo tracking. Such approaches have already refined our understanding of the alloimmune response and are pointing to new ways to improve allograft outcomes in the clinic.
Topics: Allografts; Animals; B-Lymphocytes; Graft Rejection; Graft Survival; Histocompatibility; Humans; Immunologic Techniques; Immunosuppressive Agents; Isoantibodies; Lymphocyte Activation; Mice; Models, Animal; Organ Transplantation; Plasma Cells; Risk Factors; T-Lymphocytes; Transplantation Tolerance; Treatment Outcome
PubMed: 28604446
DOI: 10.1097/TP.0000000000001847 -
BioRxiv : the Preprint Server For... Jan 2023Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have...
Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increase RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.
PubMed: 36747702
DOI: 10.1101/2023.01.25.525560