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Frontiers in Immunology 2024
Topics: Histocompatibility; Transplantation Immunology
PubMed: 38558808
DOI: 10.3389/fimmu.2024.1393026 -
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 -
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 -
Transfusion Mar 2024Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and...
BACKGROUND
Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors.
STUDY DESIGN AND METHODS
We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays.
RESULTS
Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens.
DISCUSSION
These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.
Topics: Young Adult; Humans; Child; Erythrocyte Transfusion; Erythrocytes; Anemia, Sickle Cell; Blood Group Antigens; Genotype; Anemia, Hemolytic, Autoimmune; Isoantibodies; Rh-Hr Blood-Group System
PubMed: 38289184
DOI: 10.1111/trf.17740 -
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 -
Immunohematology Dec 2022Variant alleles are found mainly in Afro-descendant individuals, as well as in patients with sickle cell disease (SCD). The most common variants are related to the...
Variant alleles are found mainly in Afro-descendant individuals, as well as in patients with sickle cell disease (SCD). The most common variants are related to the allele, which can generate partial e and c antigens. Although variant alleles have been extensively studied, defining their clinical significance is a difficult task. We evaluated the risk of RhCE alloimmunization as a consequence of partial antigens in patients with a positive phenotype transfused with red blood cell (RBC) units with the corresponding antigen. A retrospective study was performed with Brazilian patients, evaluating the number of antigen-positive transfused RBC units (incompatible due to partial antigen) in 27 patients with SCD carrying variant alleles who did not develop antibodies as well as evaluating the variants present in 12 patients with partial phenotype and correlated antibody (one patient with SCD and 11 patients with other pathologies). Two patients showed variant alleles with molecular changes that had not yet been described. Variant alleles were identified in a previous study using molecular methods. was the most frequent allele found among the patients without antibodies. Six patients with partial c antigen had a mean of 3.8 c+ RBC units transfused, and 10 patients with partial e antigen were exposed for a mean of 7.2 e+ RBC units. Among the variant alleles found in alloimmunized patients, the most frequent was which was found in five patients; the antibodies developed were anti-hr and/or anti-c. Our results showed that is indeed the most frequent variant allele in our cohort of patients with SCD, but the partial antigens that were identified have low risk of alloimmunization. is the most impactful variant in the Brazilian population with high risk of alloimmunization and clinically significant anti-hr formation.
Topics: Humans; Rh-Hr Blood-Group System; Alleles; Brazil; Retrospective Studies; Anemia, Hemolytic, Autoimmune; Isoantibodies; Anemia, Sickle Cell
PubMed: 36789463
DOI: 10.21307/immunohematology-2022-054 -
Transplantation Reviews (Orlando, Fla.) Jan 2023Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Although an improvement in graft survival has been observed in the last... (Review)
Review
Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Although an improvement in graft survival has been observed in the last decades with the use of different immunosuppressive drugs, this is still limited in time with antibody-mediated rejection being a main cause of graft-loss. Immune monitoring and risk assessment of antibody-mediated rejection before and after kidney transplantation with useful biomarkers is key to tailoring treatments to achieve the best outcomes. Here, we provide a review of the rationale and several accessible tools for immune monitoring, from the most classic to the modern ones. Finally, we end up discussing a practical proposal for alloimmune risk assessment in kidney transplantation, including histocompatibility leukocyte antigen (HLA) and non-HLA antibodies, HLA molecular mismatch analysis and characterization of peripheral blood immune cells.
Topics: Humans; Kidney Transplantation; Graft Rejection; Antibodies; Histocompatibility; HLA Antigens; Risk Assessment; Histocompatibility Testing; Graft Survival
PubMed: 36572001
DOI: 10.1016/j.trre.2022.100745 -
British Journal of Haematology Feb 2021Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by... (Review)
Review
Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by maternal red cell alloimmunisation, with IgG antibodies crossing the placenta to destroy fetal erythroid cells expressing the involved antigen. Intrauterine fetal blood transfusion is the therapy of choice for severe fetal anaemia. Despite a strong evidence base and technical advances, invasive fetal therapy carries risk of miscarriage and preterm birth. Procedure-related risks are increased when invasive, in utero transfusion is instituted prior to 22 weeks to treat severe early-onset fetal anaemia. This review focuses upon this cohort of HDFN and discusses intravenous immunoglobin (IVIg) and novel monoclonal antibody (M281, nipocalimab) treatments which, if started at the end of the first trimester, may attenuate the transplacental passage and fetal effects of IgG antibodies. Such therapy has the ability to improve fetal survival in this severe presentation of HDFN when early in utero transfusion may be required and may have wider implications for the perinatal management in general.
Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Blood Transfusion, Intrauterine; Female; Fetal Diseases; Humans; Immunoglobulins, Intravenous; Immunomodulation; Infant, Newborn; Infant, Newborn, Diseases; Plasma Exchange; Pregnancy
PubMed: 32794242
DOI: 10.1111/bjh.17041 -
Hematology, Transfusion and Cell Therapy 2024Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide. The treatment often requires phenotype-matched red blood cell (RBC) transfusions, but...
INTRODUCTION
Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide. The treatment often requires phenotype-matched red blood cell (RBC) transfusions, but alloimmunization to non-ABO antigens may occur in a part of the SCD patients. The genotyping has been used for RBC antigen prediction, reducing the possibility of the alloimmunization.
OBJECTIVE AND METHOD
In this study we performed the genotyping for the Kell and RHCE blood groups in samples from 77 phenotyped Brazilian SCD patients, whose alloimmunization profiles were also assessed.
RESULTS
Discrepancies between genotyping and phenotyping for the RHCE and Kell blood groups systems were observed in 22.07% (17/77) of the SCD patients. We found C/c and E/e discrepancies in 11.68% and 9.09% of patients, respectively; one SCD patient (1.3%) presented a discrepancy in the Kell group. Two SCD patients with discrepancies between genotype and phenotype were alloimmunized. In total, twenty-eight patients (36.4%) developed alloantibodies, of which 55.17% were directed against antigens in the Rh system, 8.62% were directed against antigens in the Kell system and 36.20%, against other groups. Finally, the frequency of discrepancies is significantly higher in non-alloimmunized patients (30.61%), compared to alloimmunized patients (7.14%) (p = 0.0217).
CONCLUSION
In part, the alloimmunization of the SCD patients may have been triggered by these discrepancies, indicating that the integration of serological and molecular tests in the immunohematology routine could help to increase the transfusion safety. However, the higher number of alloimmunized patients without discrepancies showed that reasons other than the discrepancies appear to have influenced more strongly the alloimmunization in the SCD patients in this study.
PubMed: 37344342
DOI: 10.1016/j.htct.2023.05.004