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International Journal of General... 2022Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require...
PURPOSE
Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require multiple blood transfusions, which may lead to alloimmunization because of mismatched blood group antigens. In this study, we examined the alloimmunization and autoimmunization rates in patients with SCD and thalassemia together with the involved antibodies.
PATIENTS AND METHODS
A cross-sectional study was conducted to review the transfusion history records of patients with SCD and thalassemia at Prince Mohammed bin Nasser Hospital, Jazan Province, Saudi Arabia.
RESULTS
Four-hundred thirty-eight patients (385 with SCD, 52 with β-thalassemia, and 1 with α-thalassemia) were received leukoreduced red cell transfusions. The alloimmunization and autoimmunization rates in patients with SCD were 12.98% and 0.52%, respectively. In patients with thalassemia, the alloimmunization and autoimmunization rates were 13.21% and 3.77%, respectively. The most prevalent antibodies in the study population were anti-E (17.19%) and anti-K (14.06%).
CONCLUSION
The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fy, Fy, Jk and Jk antigens in the screening panel. This will benefit patients to ensure better transfusion practices.
PubMed: 35450032
DOI: 10.2147/IJGM.S360320 -
Annual Review of Pathology Jan 2023While red blood cell (RBC) transfusion is the most common medical intervention in hospitalized patients, as with any therapeutic, it is not without risk. Allogeneic RBC... (Review)
Review
While red blood cell (RBC) transfusion is the most common medical intervention in hospitalized patients, as with any therapeutic, it is not without risk. Allogeneic RBC exposure can result in recipient alloimmunization, which can limit the availability of compatible RBCs for future transfusions and increase the risk of transfusion complications. Despite these challenges and the discovery of RBC alloantigens more than a century ago, relatively little has historically been known regarding the immune factors that regulate RBC alloantibody formation. Through recent epidemiological approaches, in vitro-based translational studies, and newly developed preclinical models, the processes that govern RBC alloimmunization have emerged as more complex and intriguing than previously appreciated. Although common alloimmunization mechanisms exist, distinct immune pathways can be engaged, depending on the target alloantigen involved. Despite this complexity, key themes are beginning to emerge that may provide promising approaches to not only actively prevent but also possibly alleviate the most severe complications of RBC alloimmunization.
Topics: Humans; Erythrocytes; Transfusion Reaction; Isoantibodies; Erythrocyte Transfusion
PubMed: 36351365
DOI: 10.1146/annurev-pathol-042320-110411 -
Transfusion Sep 2017The pathogenesis of alloimmunization is not well understood, and initiatives that aim to reduce the incidence of alloimmunization are generally expensive and either... (Review)
Review
BACKGROUND
The pathogenesis of alloimmunization is not well understood, and initiatives that aim to reduce the incidence of alloimmunization are generally expensive and either ineffective or unproven. In this review, we summarize the current medical literature regarding alloimmunization in the sickle cell disease (SCD) population, with a special focus on the financial implications of different approaches to prevent alloimmunization.
STUDY DESIGN AND METHODS
A review of EMBASE and MEDLINE data from January 2006 through January 2016 was conducted to identify articles relating to complications of SCD. The search was specifically designed to capture articles that evaluated the costs of various strategies to prevent alloimmunization and its sequelae.
RESULTS
Currently, there is no proven, inexpensive way to prevent alloimmunization among individuals with SCD. Serologic matching programs are not uniformly successful in preventing alloimmunization, particularly to Rh antigens, because of the high frequency of variant Rh alleles in the SCD population. A genotypic matching program could offer some cost savings compared to a serologic matching program, but the efficacy of gene matching for the prevention of alloimmunization is largely unproven, and large-scale implementation could be expensive.
CONCLUSIONS
Future reductions in the costs associated with genotype matching could make a large-scale program economically feasible. Novel techniques to identify patients at highest risk for alloimmunization could improve the cost effectiveness of antigen matching programs. A clinical trial comparing the efficacy of serologic matching to genotype matching would be informative.
Topics: Anemia, Sickle Cell; Blood Group Incompatibility; Blood Grouping and Crossmatching; Blood Transfusion; Cost-Benefit Analysis; Genotype; Humans; Transfusion Reaction
PubMed: 28653325
DOI: 10.1111/trf.14212 -
Circulation Research Sep 2020Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to...
RATIONALE
Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to contribute to this process, the complex cellular heterogeneity within the grafts, and the underlying mechanisms regulating the disease progression remain largely uncharacterized.
OBJECTIVE
We aimed to delineate the cellular heterogeneity within the allografts, and to explore possible mechanisms underlying this process.
METHODS AND RESULTS
Here, we reported the transcriptional profiling of 11 868 cells in a mouse model of transplant arteriosclerosis by single-cell RNA sequencing. Unbiased clustering analyses identified 21 cell clusters at different stages of diseases, and focused analysis revealed several previously unknown subpopulations enriched in the allografts. Interestingly, we found evidence of the local formation of tertiary lymphoid tissues and suggested a possible local modulation of alloimmune responses within the grafts. Intercellular communication analyses uncovered a potential role of several ligands and receptors, including and , in regulating lymphatic endothelial cell-induced early chemotaxis and infiltration of immune cells. In vivo mouse experiments confirmed the therapeutic potential of CCL21 and CXCR3 neutralizing antibodies in transplant arteriosclerosis. Combinational use of genetic lineage tracing and single-cell techniques further indicate the infiltration of host-derived c-Kit stem cells as heterogeneous populations in the allografts. Finally, we compared the immune response between mouse allograft and atherosclerosis models in single-cell RNA-seq analysis. By analyzing susceptibility genes of disease traits, we also identified several cell clusters expressing genes associated with disease risk.
CONCLUSIONS
Our study provides a transcriptional and cellular landscape of transplant arteriosclerosis, which could be fundamental to understanding the initiation and progression of this disease. CCL21/CXCR3 was also identified as important regulators of immune response and may serve as potential therapeutic targets in disease treatment.
Topics: Animals; Aorta; Arteriosclerosis; Cell Lineage; Chemokine CCL21; Disease Models, Animal; Female; Gene Expression Profiling; Graft Survival; Immunity, Cellular; Immunity, Innate; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Proto-Oncogene Proteins c-kit; RNA-Seq; Receptors, CXCR3; Single-Cell Analysis; Time Factors; Transcriptome; Transplantation Tolerance
PubMed: 32689904
DOI: 10.1161/CIRCRESAHA.119.316470 -
Transfusion Medicine and Hemotherapy :... Oct 2018Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA... (Review)
Review
BACKGROUND AND OBJECTIVE
Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA systems are assigned, and during the last decades enormous efforts have been undertaken to identify the underlying genes and to characterize the antigens. This review of the literature will provide the current genetic, molecular and functional information on HNAs.
RECENT FINDINGS
New information on alleles and antigens has been added to nearly each of the five HNA systems. HNA-1d has been added as the antithetical epitope to HNA-1c that is located on the glycoprotein encoded by but not by and now are included as new alleles. A substitution was demonstrated as the main reason for the HNA-2-negative phenotype on neutrophils. The target glycoprotein of HNA-3 antibodies could be identified as choline transporter-like protein 2 (CTL2) encoded by The conformation sensitive epitope discriminates between arginine and glutamine at position 152 resulting in HNA-3a and HNA-3b. An additional Leu151Phe substitution can impair HNA-3a antibody binding. Recently an alloantibody against HNA-4b which discriminates from HNA-4a by an Arg61His exchange of the glycoprotein encoded by the gene was reported in neonatal alloimmune neutropenia. An update of the current HNA nomenclature based on the new findings was provided in 2016 by the ISBT Granulocyte Immunobiology Working Party nomenclature subcommittee.
CONCLUSIONS
The molecular basis of each of the five HNA antigen systems has been decoded during the past decades. This enables reliable molecular typing strategies, antibody detection and specification as well as development of new assays based on recombinant antigens. However, research on HNA alleles, antigens, and antibodies is not finally terminated and also in the future will add new findings.
PubMed: 30498408
DOI: 10.1159/000491031 -
Journal of Medicine and Life Jul 2023The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus... (Meta-Analysis)
Meta-Analysis Review
The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus and newborn. This systematic review discusses the prevalence of RhD variants among pregnant women and the importance of including RhD genotyping for prenatal testing to detect RhD variants and prevent anti-D alloimmunization. A comprehensive literature search was conducted using scientific search engines, including PubMed and MEDLINE databases, with the keywords 'anti-D alloimmunization', 'RhD variant', and 'pregnant women.' The review adhered to the PRISMA guidelines. Meta-analysis was performed using MedCalc version 20. A significance level of p≤0.05 was considered statistically significant for all two-tailed tests. The meta-analysis included four articles that met the inclusion criteria. The total prevalence of RhD positivity (RhD+) was 61% (95% CI:34%-85%). The prevalence ranged from 22% to 82%, indicating a high degree of heterogeneity between studies (I2=98.71%, p<0.0001). The overall prevalence of D variants was 15% (95% CI, 9%-23%) with a prevalence of 0.05% to 100%, showing a high degree of heterogeneity between studies (I2=99.89%, p<0.0001). Anti-D alloimmunization could occur in pregnant women with some types of RhD variants. All four studies focused on molecular testing of samples showing inconsistent or weak results with at least two anti-D antibodies using serological methods.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnant Women; Fetus; Prevalence
PubMed: 37900088
DOI: 10.25122/jml-2023-0004 -
Current Opinion in Organ Transplantation Dec 2019The microbiota in mammalian hosts can affect maturation and function of the immune system and has been associated with health and disease. We will review new findings on... (Review)
Review
PURPOSE OF REVIEW
The microbiota in mammalian hosts can affect maturation and function of the immune system and has been associated with health and disease. We will review new findings on how this dynamic environmental factor impacts alloimmunity and therapy in transplant hosts.
RECENT FINDINGS
The microbiota changes after transplantation and immunosuppressive therapy. New data indicate that different microbial community structures have distinct impact on graft outcome, from promoting, to inhibiting or being neutral to transplant survival. In addition, we will address reciprocal interactions between the microbiota and immunosuppressive drugs, as well as the suitability of the microbiota as a predictive biomarker and its utility as adjunct therapy in transplantation.
SUMMARY
Advances in microbiome sequencing and wider availability of gnotobiotic facilities are enabling mechanistic investigations into the commensal communities and pathways that modulate allograft outcome, responsiveness to immunosuppression and side effects of drugs. A better understanding of the functions of the microbiota may help mitigate drug toxicity, predict drug dosage and dampen alloimmunity in transplant patients.
Topics: Graft Survival; Humans; Microbiota; Organ Transplantation
PubMed: 31577594
DOI: 10.1097/MOT.0000000000000702 -
Transfusion Medicine Reviews Jan 2021Red blood cell (RBC) transfusion to neonates is thought to rarely provoke an immune response. Neonatal testing guidelines suggest that antibody screening is not... (Review)
Review
Red blood cell (RBC) transfusion to neonates is thought to rarely provoke an immune response. Neonatal testing guidelines suggest that antibody screening is not necessary when the mother has no antibodies. Alternatively, maternal blood samples can be used for antibody screening and cross-matching. However, the guidelines are based on small-scale studies of white-dominant populations. Furthermore, transfusion-related alloimmunization is less well established among children and adolescents as a whole among Japanese and East Asians. To elucidate the incidence of transfusion-related alloimmunization among neonates, children, and adolescents, and whether current guidelines are applicable to Japanese populations, a nationwide retrospective multicenter cohort survey was conducted in 50 tertiary-care hospitals in Japan. Between 2001 and 2015 inclusive, recipients of at least 1 allogeneic RBC transfusion were categorized into groups A-F according to their age at the time of transfusion: (A) neonates <1 month; (B) infants 1 to <12 months; (C) children 1 to <5 years; (D) prepubescents 5 to <10 years; (E) young pubescents 10 to <15 years; and (F) adolescents/young adults 15 to <20 years. Excluding maternally derived antibodies and naturally occurring, cold-reactive, and/or nonspecific antibodies, 69 (0.61%) of 11350 RBC recipients <20 years old formed at least 1 clinically significant alloantibody. The alloimmunization rate differed significantly (P < .0001) by age: none (0%) of 3407 in group A; 11 (0.46%) of 2410 in group B; 18 (0.76%) of 2361 in group C; 9 (0.80%) of 1119 in group D; 12 (1.15%) of 1043 in group E; and 19 (1.88%) of 1010 in group F. Clearly different incidences of alloimmunization emerged in group A compared to B, C, D, E, or F, as confirmed by logistic regression analysis adjusted by numbers of donor exposure. Alloimmunization did not occur from RBC transfusions within the first month of life and rarely occurred (0.46%-0.80%) after transfusion within the first decade of life. Alloimmunization occurred in 1.15%-1.88% of young pubescents and adolescents/young adults. These findings support the use of guidelines developed in Europe and the United States for East Asian pediatric recipients.
Topics: Adolescent; Adult; Blood Transfusion; Child; Erythrocyte Transfusion; Erythrocytes; Humans; Isoantibodies; Japan; Multicenter Studies as Topic; Retrospective Studies; Young Adult
PubMed: 33012576
DOI: 10.1016/j.tmrv.2020.09.001 -
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 :... Nov 2014Red blood cell (RBC) alloimmunization may occur following transfusion or pregnancy/delivery. Although observational human studies have described the immunogenicity of... (Review)
Review
Red blood cell (RBC) alloimmunization may occur following transfusion or pregnancy/delivery. Although observational human studies have described the immunogenicity of RBC antigens and the clinical significance of RBC alloantibodies, studies of factors influencing RBC alloimmunization in humans are inherently limited by the large number of independent variables involved. This manuscript reviews data generated in murine models that utilize transgenic donor mice, which express RBC-specific model or authentic human blood group antigens. Transfusion of RBCs from such donors into nontransgenic but otherwise genetically identical recipient mice allows for the investigation of individual donor or recipient-specific variables that may impact RBC alloimmunization. Potential donor-related variables include methods of blood product collection, processing and storage, donor-specific characteristics, RBC antigen-specific factors, and others. Potential recipient-related variables include genetic factors (MHC/HLA type and polymorphisms of immunoregulatory genes), immune activation status, phenotype of regulatory immune cell subsets, immune cell functional characteristics, prior antigen exposures, and others. Although murine models are not perfect surrogates for human biology, these models generate phenomenological and mechanistic hypotheses of RBC alloimmunization and lay the groundwork for follow-up human studies. Long-term goals include improving transfusion safety and minimizing the morbidity/mortality associated with RBC alloimmunization.
PubMed: 25670928
DOI: 10.1159/000368995