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BACKGROUND AND OBJECTIVES: Pregnancy in women with sickle cell disease (SCD) is associated with severe complications. Red blood cell (RBC) alloimmunisation is a worrying situation in pregnant women with SCD. This could increase the difficulty in finding a pheno-compatible red blood product. Our study aimed to determine the prevalence of RBC alloantibodies in pregnant women with SCD and to determine the risk factors for alloantibodies formation. METHODS/MATERIALS: We conducted a prospective study at the "Centre National de Transfusion Sanguine de Bamako" from August 2022 to January 2023. For each participant, we collected important information, including obstetrical and transfusion histories. We performed ABO group, Rh and Kell phenotyping, and antibody screening in all study participants. We performed statistical analysis. RESULTS: We recruited 95 pregnant women with SCD. In our study, 62% of our participant had a history of blood transfusion. Only 23% of our pregnant women with SCD had a history of miscarriage. The prevalence of RBC alloantibodies was 14%. The main antibodies detected were anti-E (38%) and pan-agglutinins (23%). Miscarriage history, blood transfusion history, and pregnancy number were the main risk factors for RBC alloimmunisation. CONCLUSION: The care of pregnant women with SCD is complex and requires collaboration between haematologists, clinicians and gynaecologists. National guidelines should be implemented to make ABO and D typing, Rh and Kell phenotyping and antibody screening routine for all pregnant women. This would facilitate early detection of high-risk situations. Particular attention should be paid to SCD pregnant women with miscarriage and blood transfusion histories.
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Background: Alloimmunisation remains a major consequence of blood transfusion among sickle cell disease (SCD) and thalassemia patients due to the exposure to non-self-red blood cell (RBC) antigen. The complication is associated with transfusion reactions and delayed transfusion procedure because of the difficulty of finding compatible blood. This study aims to determine the prevalence of alloimmunisation to RBC and alloantibody specificities among SCD and thalassemia patients in, an endemic area of SCD and thalassemia, Jazan province of Saudi Arabia, from three major hospitals. Methods: This is a retrospective, multicenter cross-sectional study conducted on 1027 patients with SCD and thalassemia, which received Rh/K matched transfusions in 2019 in the three centers. Demographic data and medical records of participants from three transfusion institutions were collected and analysed. Results: A total of 1027 were enrolled in the cohort; 906 (88.2%) and 121 (11.8%) patients with SCD and thalassemia, respectively. There were 483 (47%) males and 544 (53%) females with median age of 15 (range 1-48). Among the studied population, 78 were alloimmunised with an overall alloimmunisation rate of 7.6%. These patients developed a total of 108 alloantibodies, and anti-E was the most detected antibody (25.9%) followed by anti-K (24.1%). Conclusion: The overall rate of alloimmunisation to RBC antigen among the studied population in Jazan was low compared to other areas in the country. Most alloantibodies detected were against E and K antigens. The knowledge of most encountered alloantibodies in our population will aid in selecting the most appropriate antigen-negative red cells. Further research, however, is needed to explore factors associated with residual risk of alloimmunisation in these patients.
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BACKGROUND: Rh blood group antigens are the second most important blood group antigens in clinical transfusion due to their immunogenicity and prevalence. Childbirth, miscarriage, and other obstetrics events are risk factors for alloimmunization in women which increases the likelihood of haemolytic blood transfusion reaction and hemolytic disease of the fetal/newborn (HDNF/B). Even though there are several data on the RhD status of our populations. However, there is a dearth of data on pregnant women's C, E, c, and e status, their alloimmunization risk, and rates in Nigeria. OBJECTIVES: This study aims to provide information on the distribution of the Rh major antigens and risk factors for alloimmunization in pregnant women in southwestern Nigeria. MATERIALS AND METHODS: This was a descriptive cross-sectional study of 133 pregnant women attending routine ante-natal clinics. Questionnaires were administered to collect biodata and obstetrics history. ABO blood grouping and Rh phenotyping were carried out on their blood samples using RAPID LABS Monoclonal Rhesus Typing Reagent. RESULTS AND DISCUSSION: Rh blood group antigen c was present in 100% of the women, followed by e (98.5%) and D (95.5%). C and E are the least prevalent antigens and probably the ones to which antibodies may be formed. The commonest Rh phenotype was Dce. Of all the pregnant women, alloimmunization was present in 0.8%. Of those who were RhD negative, alloimmunization was present in 16.7%. Pregnant women are more likely to be alloimmunized against C and E antigens than c and e antigens due to their low and high frequencies respectively.
CONTEXTE: Les antigènes du groupe sanguin Rh sont les seconds plus importants en transfusion clinique en raison de leur immunogénicité et de leur prévalence. L'accouchement, la fausse couche et d'autres événements obstétriques sont des facteurs de risque d'alloimmunisation chez les femmes, augmentant ainsi la probabilité de réactions hémolytiques lors de transfusions sanguines et de maladies hémolytiques du fÅtus/nouveau-né (HDNF/B). Bien qu'il existe plusieurs données sur le statut RhD de nos populations, il y a un manque de données sur le statut des antigènes C, E, c et e chez les femmes enceintes, leur risque d'alloimmunisation et les taux associés au Nigéria. OBJECTIFS: Cette étude vise à fournir des informations sur la distribution des principaux antigènes Rh et les facteurs de risque d'alloimmunisation chez les femmes enceintes dans le sud-ouest du Nigéria. MÉTHODOLOGIE: Il s'agit d'une étude descriptive transversale de 133 femmes enceintes fréquentant les cliniques prénatales de routine. Des questionnaires ont été administrés pour collecter des données biodémographiques et des antécédents obstétriques. La détermination des groupes sanguins ABO et le phénotypage Rh ont été réalisés sur leurs échantillons de sang à l'aide du réactif de typage Rh monoclonal RAPID LABS. RÉSULTATS ET DISCUSSION: L'antigène c du groupe sanguin Rh était présent chez 100 % des femmes, suivi de e (98,5 %) et D (95,5 %). Les antigènes C et E sont les moins prévalents et probablement ceux contre lesquels des anticorps peuvent être formés. Le phénotype Rh le plus courant était Dce. Parmi toutes les femmes enceintes, l'alloimmunisation était présente chez 0,8 %. Parmi celles qui étaient RhD négatives, 'alloimmunisation était présente chez 16,7 %. Les femmes enceintes sont plus susceptibles de développer une alloimmunisation contre les antigènes C et E que contre les antigènes c et e en raison de leurs fréquences respectives faibles et élevées. MOTS-CLÉS: Antigènes du groupe sanguin Rh, Phénotype, Alloanticorps érythrocytaires, Femmes enceintes.
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Isoinmunización Rh , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Femenino , Nigeria/epidemiología , Embarazo , Estudios Transversales , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Adulto , Isoinmunización Rh/epidemiología , Isoinmunización Rh/inmunología , Factores de Riesgo , Adulto Joven , Sistema del Grupo Sanguíneo ABO/inmunología , Prevalencia , Adolescente , Tipificación y Pruebas Cruzadas Sanguíneas/métodosRESUMEN
Background: Immune tolerance induction (ITI) is the treatment of choice to eradicate neutralizing anti-factor (F)VIII alloantibodies (inhibitors) in people with inherited hemophilia A. However, it is not successful in 10% to 40% of the cases. The biological mechanisms and biomarkers associated with ITI outcome are largely unknown. Objectives: The aim of this study was to investigate the association of plasma cytokines (interferon-γ, tumor necrosis factor, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-10, and IL-17A), chemokines (IL-8/CXCL8, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IP-10/CXCL10), and anti-FVIII immunoglobulin (Ig) G total, IgG1, and IgG4 with ITI outcome. Methods: In this cross-sectional analysis of the Brazilian Immune Tolerance Study, we assessed plasma levels of anti-FVIII IgGs using an enzyme-linked immunosorbent assay with plasma-derived FVIII and recombinant FVIII as target antigens, immobilized in microplates. Results: We assayed 98 plasma samples of moderately severe and severe (FVIII activity, <2%) people with hemophilia A after completion of a first ITI course. Levels of anti-recombinant FVIII IgG total and IgG4 were higher in people with hemophilia A who failed ITI (IgG total optical density [OD], 0.37; IQR, 0.15-0.73; IgG4 OD, 2.19; IQR, 0.80-2.52) than in those who had partial (IgG total OD, 0.03; IQR, 0.00-0.14; IgG4 OD, 0.39; IQR, 0.09-1.11; P < .0001 for both) or complete success (IgG total OD, 0.04; IQR, 0.00-0.07; IgG4 OD, 0.07; IQR, 0.06-0.40; P < .0001 for both). Plasma cytokines, chemokines, and anti-FVIII IgG1 were not associated with ITI outcome. Conclusion: Our results show that high levels of plasma anti-FVIII IgG4 and IgG total are associated with ITI failure.
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OBJECTIVE: We report a rare case of acute hemolytic reactions caused by immunoglobulin (Ig)M anti-M antibody and present a literature review. CASE REPORT: A 61-year-old male patient who underwent blood transfusion developed fever, chills, soy sauce-colored urine, and changes in laboratory test results, including persistently decreased hemoglobin levels, neutrophilia, elevated lactate dehydrogenase level, acute kidney injury, mild acute liver injury, and activation of the coagulation system, indicating acute hemolytic transfusion reaction (AHTR). Antibody screening and major crossmatching results indicated weak positive at 37°C for both posttransfusion and pretransfusion sample. Subsequent serological examinations indicated the presence of IgM anti-M antibodies in plasma but the direct antiglobulin and elution tests were negative. Antibody hemolytic activity assay confirmed AHTR caused by anti-M. The transfused red blood cells were MM and the patient is NN. These signs and symptoms disappeared rapidly and required no additional interventions before discharge. CONCLUSION: The accurate diagnosis of anti-M antibody-mediated acute hemolysis is essential for guiding treatment decisions.
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Background: Von Willebrand disease (VWD) type 3 is characterized by a complete deficiency of von Willebrand factor (VWF), resulting in a severe bleeding phenotype. Treatment often requires administration of VWF concentrates/factor (F)VIII. However, the development of alloantibodies is a rare complication, resulting in ineffective recovery and allergic reactions. Emicizumab, a bispecific antibody mimicking FVIII function, has emerged as a potential alternative, with promising results reported in several case reports. Key Clinical Question: Description of multiple approaches to control highly severe postpartum hemorrhage in type 3 VWD with alloantibodies, including off-label use of emicizumab. Clinical Approach: Here we present a 28-year-old patient with type 3 VWD and alloantibodies, known to have arthropathy of the right elbow. Previous immune tolerance induction was unsuccessful. Despite receiving negative pregnancy advice during preconception counseling, the patient became pregnant. Delivery was induced at 38 4/7 weeks with prostaglandin, and recombinant FVIIa (rFVIIa) was administered every 2 hours. Despite administration of rFVIIa, bleeding persisted, requiring manual placental removal and insertion of a Bakri balloon. Since bleeding persisted, plasma-derived VWF was administered with an initial excellent recovery and successful embolization of the uterine artery. Twelve days postpartum, she developed endometritis and recurrent vaginal bleeding treated with antibiotics, rFVIIa every 2 hours, and multiple erythrocyte transfusions. Plasma-derived VWF was administered but was complicated by anaphylaxis and no recovery. Due to persistent vaginal bleeding, reembolization of uterine arteries was performed and off-label emicizumab was initiated. Twenty-nine days postpartum, she developed septic shock requiring an abdominal hysterectomy, again complicated by severe bleeding necessitating direct intraabdominal packing after rFVIIa. A computed tomography scan 9 days postsurgery revealed thrombosis in the left iliac vein and asymptomatic pulmonary embolisms. rFVIIa was stopped and prophylactic low-molecular-weight heparin was started. The patient was discharged 2 months after delivery on low-dose low-molecular-weight heparin, emicizumab, and antibiotics for an intra-abdominal abscess. During 2.5 years of emicizumab prophylaxis, she has had no rebleeding in her arthropathic right elbow. Conclusion: The current case emphasizes the postpartum clinical challenges of patients with type 3 VWD and alloantibodies. It underscores the potential role of emicizumab in maintaining hemostatic control.
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BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a condition during pregnancy, which can lead to thrombocytopenia and a bleeding tendency with intracranial hemorrhage (ICH) being the most concerning complication in the fetus or neonate. An incompatibility between human platelet antigen (HPA)-1a accounts for the majority of FNAIT cases. Binding of HPA-1a-specific alloantibodies to their target on fetal platelets and endothelial cells can induce apoptosis of megakaryocytes, disrupt platelet function, and impair angiogenesis. Currently, there is no screening program to identify pregnancies at risk for severe disease. A better understanding of HPA-1a-specific antibody heterogeneity in FNAIT could aid in identifying pathogenic antibody properties linked to severe disease. STUDY DESIGN AND METHODS: This study aimed to isolate HPA-1a-specific B-cells from an HPA-1a-alloimmunized pregnant woman. Using fluorescently labeled HPA-1a-positive platelets, single B-cells were sorted and cultured for 10 days to stimulate antibody production. Subsequently, supernatants were tested for the presence of antibodies by enzyme-linked immunosorbent assay and their reactivity towards HPA-1a-positive platelets. Amplification and sequencing of variable regions allowed the generation of monoclonal antibodies using a HEK-Freestyle-based expression system. RESULTS: Three platelet-specific B-cells were obtained and cloned of which two were specific for HPA-1a, named D- and M-204, while the third was specific for HLA class I, which was named L-204. DISCUSSION: This study outlined an effective method for the isolation of HPA-1a-specific B-cells and the generation of monoclonal antibodies. Further characterization of these antibodies holds promise for better understanding the pathogenic nature of alloantibodies in FNAIT.
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Antígenos de Plaqueta Humana , Isoanticuerpos , Trombocitopenia Neonatal Aloinmune , Humanos , Antígenos de Plaqueta Humana/inmunología , Embarazo , Femenino , Trombocitopenia Neonatal Aloinmune/inmunología , Isoanticuerpos/inmunología , Integrina beta3/inmunología , Linfocitos B/inmunología , Anticuerpos Monoclonales/inmunología , Plaquetas/inmunología , Plaquetas/metabolismo , Recién NacidoRESUMEN
An adult domestic short-haired feline leukemia virus-infected cat was referred for kidney failure and worsening anemia requiring transfusions. ABC blood typing was performed with an immunochromatographic strip assay at different occasions. Gel column systems were used for the major and minor crossmatching tests, and anti-A and anti-B titers were determined. No discrete A or B bands appeared on the immunochromatographic strips at any time point for the recipient cat. The recipient's plasma agglutinated RBCs from tested type A and B cats. The recipient's RBCs appeared compatible with plasma from 1 type A and 2 B donors, and incompatible with plasma from another type A cat. Genotyping of recipient blood revealed a single homozygous c.179G>T CMAH variant predicting a blood type B. These studies suggest an unusual weak type B or missing all ABC antigens. The latter resembles the exceedingly rare Bombay phenotype in the human ABO blood group system.
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Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión Sanguínea , Animales , Gatos , Humanos , Tipificación y Pruebas Cruzadas Sanguíneas/veterinaria , Transfusión Sanguínea/veterinaria , Sistema del Grupo Sanguíneo ABO/genética , Anticuerpos , Genotipo , FenotipoRESUMEN
K-associated anemic disease of the fetus and newborn (K-ADFN) is a rare but life-threatening disease in which maternal alloantibodies cross the placenta and can mediate an immune attack on fetal red blood cells expressing the K antigen. A considerably more common disease, D-associated hemolytic disease of the fetus and newborn (D-HDFN), can be prophylactically treated using polyclonal α-D antibody preparations. Currently, no such prophylactic treatment exists for K-associated fetal anemia, and disease is usually treated with intrauterine blood transfusions. Here we review current understanding of the biology of K-associated fetal anemia, how the maternal immune system is sensitized to fetal red blood cells, and what is understood about potential mechanisms of prophylactic HDFN interventions. Given the apparent challenges associated with preventing alloimmunization, we highlight novel strategies for treating sensitized mothers to prevent fetal anemia that may hold promise not only for K-mediated disease, but also for other pathogenic alloantibody responses.
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Anemia , Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Enfermedades Hematológicas , Embarazo , Femenino , Recién Nacido , Humanos , Eritroblastosis Fetal/prevención & control , Anemia/etiología , Anemia/prevención & control , IsoanticuerposRESUMEN
Nonhuman primates are the closest animal models to humans with respect to genetics and physiology. Consequently, a critical component of immunogenetics research relies on drawing inferences from the cynomolgus macaque to inform human trials. Despite the conserved organization of the Major Histocompatibility Complex (MHC) between cynomolgus macaques and humans, MHC genotyping of cynomolgus macaques is challenging due to high rates of copy number variants, duplications, and rearrangements, particularly at the MHC class I loci. Furthermore, the limited availability of commercial reagents specific to cynomolgus macaques that can be used to characterize anti-MHC class I and class II antibody (Ab) specificities in cynomolgus macaques presents a major bottleneck in translational research. Here we successfully characterized cynomolgus macaque Mafa class I and class II serologic specificities in 86 animals originating from various geographical regions using the complement dependent cytotoxicity (CDC) assay with human HLA class I and class II monoclonal antibody (mAb) typing trays. Further, we successfully induced and characterized anti-Mafa class I and class II alloantibody specificity using HLA single antigen bead assays. We also subsequently tracked the alloAb burden in the animals during treatment with anti-B lymphocyte stimulator (BLyS) treatment. Altogether, these methods can be easily used in translational research to serotype MHC class I and class II specificity in macaques, characterize their alloAb specificity, and evaluate the efficacy of novel therapeutic modalities in depleting circulating alloAbs in these animals.
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Complejo Mayor de Histocompatibilidad , Polimorfismo Genético , Animales , Humanos , Alelos , Antígenos de Histocompatibilidad Clase I/genética , Macaca fascicularis/genéticaRESUMEN
Introduction: Alloimmunization is common following platelet transfusion and can result in negative outcomes for recipients such as refractoriness to subsequent transfusions and rejection of transplants. Healthy people do not receive blood transfusions, and the diseases and therapies that result in a need to transfuse have significant impacts on the immunological environment to which these alloantigens are introduced. Ablative chemotherapies are common among platelet recipients and have potent immunological effects. In this study, we modeled the impact of chemotherapy on the alloresponse to platelet transfusion. As chemotherapies are generally regarded as immunosuppressive, we hypothesized that that they would result in a diminished alloresponse. Methods: Mice were given a combination chemotherapeutic treatment of cytarabine and doxorubicin followed by transfusion of allogeneic platelets, and compared to controls given no treatment, chemotherapy alone, or transfusion alone. Alloantibody responses were measured 2 weeks after transfusion, and cellular responses and growth factors were monitored over time. Results: Contrary to our hypothesis, we found that chemotherapy led to increased alloantibody responses to allogeneic platelet transfusion. This enhanced response was antigen-specific and was associated with increased CD4+ and CD8+ T cell responses. Chemotherapy led to rapid lymphocyte depletion followed by reconstitution, non-specific activation of transitional B cells with the highest levels of activation in the least mature subsets, and increased serum levels of B cell activating factor (BAFF). Conclusion: These data suggest that ablative chemotherapy can increase the risk of alloimmunization and, if confirmed clinically, that additional measures to protect these patient populations may be warranted.
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Plaquetas , Transfusión de Plaquetas , Ratones , Humanos , Animales , Transfusión de Plaquetas/efectos adversos , Transfusión Sanguínea , Isoanticuerpos , Interleucina-4RESUMEN
Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs). We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation. We find that treatment of allo-sensitized hosts with CAR T cells targeting Bmems and LLPCs eliminates donor-specific allo-antibodies (DSAs) and mitigates hyperacute rejection of subsequent islet allografts. We then assess the clinical efficacy of the CAR T therapy for desensitization in patients with multiple myeloma (MM) with pre-existing HLA allo-antibodies who were treated with the combination of CART-BCMA and CART-19 (ClinicalTrials.gov: NCT03549442) and observe clinically meaningful allo-antibody reduction. These findings provide logical rationale for clinical evaluation of CAR T-based immunotherapy in highly sensitized candidates to promote successful transplantation.
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Receptores Quiméricos de Antígenos , Humanos , Animales , Ratones , Células Plasmáticas , Antígeno de Maduración de Linfocitos B , Linfocitos T , Inmunoterapia , AnticuerposRESUMEN
Introduction: Alloimmune responses against platelet antigens, which dominantly target the major histocompatibility complex (MHC), can cause adverse reactions to subsequent platelet transfusions, platelet refractoriness, or rejection of future transplants. Platelet transfusion recipients include individuals experiencing severe bacterial or viral infections, and how their underlying health modulates platelet alloimmunity is not well understood. Methods: This study investigated the effect of underlying inflammation on platelet alloimmunization by modelling viral-like inflammation with polyinosinic-polycytidylic acid (poly(I:C)) or gram-negative bacterial infection with lipopolysaccharide (LPS), hypothesizing that underlying inflammation enhances alloimmunization. Mice were pretreated with poly(I:C), LPS, or nothing, then transfused with non-leukoreduced or leukoreduced platelets. Alloantibodies and allogeneic MHC-specific B cell (allo-B cell) responses were evaluated two weeks later. Rare populations of allo-B cells were identified using MHC tetramers. Results: Relative to platelet transfusion alone, prior exposure to poly(I:C) increased the alloantibody response to allogeneic platelet transfusion whereas prior exposure to LPS diminished responses. Prior exposure to poly(I:C) had equivalent, if not moderately diminished, allo-B cell responses relative to platelet transfusion alone and exhibited more robust allo-B cell memory development. Conversely, prior exposure to LPS resulted in diminished allo-B cell frequency, activation, antigen experience, and germinal center formation and altered memory B cell responses. Discussion: In conclusion, not all inflammatory environments enhance bystander responses and prior inflammation mediated by LPS on gram-negative bacteria may in fact curtail platelet alloimmunization.
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Lipopolisacáridos , Transfusión de Plaquetas , Ratones , Animales , Transfusión de Plaquetas/efectos adversos , Lipopolisacáridos/farmacología , Poli C , Ratones Endogámicos BALB C , Antígenos de Histocompatibilidad , Inflamación/etiología , Poli I-C/farmacologíaRESUMEN
Belatacept is the first costimulatory blockade agent clinically approved for transplant immunosuppression. Although more than 10 years of study have demonstrated that belatacept offers superior long-term renal allograft and patient survival compared to conventional calcineurin inhibitor (CNI)-based immunosuppression regimens, the clinical adoption of belatacept has continued to lag because of concerns of an early risk of acute cellular rejection (ACR) and various logistical barriers to its administration. In this review, the history of the clinical development of belatacept is examined, along with the findings of the seminal BENEFIT and BENEFIT-EXT trials culminating in the clinical approval of belatacept. Recent efforts to incorporate belatacept into novel CNI-free immunosuppression regimens are reviewed, as well as the experience of the Emory Transplant Center in using a tapered course of low-dose tacrolimus in belatacept-treated renal allograft patients to garner the long-term outcome benefits of belatacept without the short-term increased risks of ACR. Potential avenues to increase the clinical adoption of belatacept in the future are explored, including surmounting the logistical barriers of belatacept administration through subcutaneous administration or more infrequent belatacept dosing. In addition, belatacept conversion strategies and potential expanded clinical indications of belatacept are discussed for pediatric transplant recipients, extrarenal transplant recipients, treatment of antibody-mediated rejection (AMR), and in patients with failed renal allografts. Finally, we discuss the novel immunosuppressive drugs currently in the development pipeline that may aid in the expansion of costimulation blockade utilization.
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BACKGROUND AND OBJECTIVES: Screening for red blood cell alloantibodies (RBC-Ab) is a critical step in ensuring blood transfusion safety performed by blood donation screening laboratories. We aim to evaluate the prevalence of the RBC-Ab among healthy blood donors. MATERIALS AND METHODS: Antibody screening of serum of all voluntary blood donors was performed as a routine immune-haematological procedure by a solid-phase method on a fully automated immunohaematology analyser. Positive sera were further investigated to identify the specificity of RBC-Ab by a commercially available red cell panel. RESULTS: Between January 2012 and December 2021, a total of 212,218 donations were screened for the presence of RBC-Ab, 74% from male donors (n = 157,898) and 26% from female donors (n = 54,320). Mean age at donation time was 32 ± 12 years. A total of 1007 donations were screened positive (0.47%), and 131 were confirmed positive for alloantibodies in their serum, yielding a prevalence of 0.06% (95% confidence interval: 0.05-0.07). Most frequent alloantibodies identified were of RH blood group system (64%), followed by anti-MNS (19%), anti-Kidd and Lewis (6% each) and anti-KEL (4%). The results showed a statistically higher prevalence of alloantibodies in women than men. Our results showed a lower prevalence as compared to the available data, which might be related to our study population. CONCLUSION: The prevalence of positive antibody screening in healthy donors in this study was found to be 0.47%, while the prevalence of alloantibodies was 0.06%. The most common alloantibodies were anti-RH1 (25%) and anti-RH3 (24%).
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Isoanticuerpos , Personal Militar , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Estudios Retrospectivos , Donantes de Sangre , Prevalencia , EritrocitosRESUMEN
BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is characterized by destruction of fetal/neonatal red blood cells (RBCs) secondary to maternally derived antibodies, which are typically thought to be passively acquired via placental transfer. Few cases have examined the possibility of HDFN mediated by maternal antibodies passively transferred via breast milk. METHODS: We describe two cases of persistent HDFN in infants potentially mediated by passively acquired antibodies via maternal breast milk. We discuss supporting and refuting evidence that may account for this possibility and describe testing methodology illustrating how maternal alloantibodies can be detected in breast milk. RESULTS: In both cases, anti-D antibodies were detected in maternal breast milk. One patient experienced a significant decrease in anti-D plasma titer from 64 to 4 dilutions following 2 weeks of breastfeeding cessation. The other patient experienced a resolution of anemia without breastfeeding cessation. CONCLUSION: There is a paucity of data regarding the lifespan of passively acquired RBC antibodies in neonatal circulation, with significant variation noted between passively acquired IgG based on studies utilizing intravenous immunoglobulin compared to studies of maternally-acquired antiviral IgG antibodies. While our data do not definitively implicate passive transfer of alloantibodies in breast milk as a mediator of HDFN, they do illustrate the need for further investigation into the mechanisms and kinetics of passively acquired antibodies in neonatal circulation.
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Anemia Hemolítica , Eritroblastosis Fetal , Recién Nacido , Humanos , Femenino , Embarazo , Isoanticuerpos , Leche Humana , Placenta , Inmunoglobulina GRESUMEN
Haemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens, which could result in fetal anaemia, hyperbilirubinaemia, kernicterus, and death. This study was designed to determine the prevalence of alloantibodies against erythrocyte antigens in blood samples of pregnant women during the first trimester which may cause HDFN. A total of 123 consenting pregnant women attending the antenatal clinic of Ekiti state University Teaching Hospital, Ado Ekiti participated in the study which lasted three months. The participants were within the ages of 16 to 45 years old across the major ethnic group in Nigeria. ABO/Rh typing, screening and identification of red blood cell alloantibodies were carried out using standard protocols. 15 (12.2%) subjects had detectable antibodies known to cause haemolytic disease of the fetus and newborn (HDFN). The specificity of the antibodies was as follows: anti-K (5, 33%), anti-k (3, 20%), anti- Jsa (2, 13%), anti-C. (3, 20%), and anti-E (2, 13 %). Based on ethnicity, the prevalence of Kell antibodies was highly significant among the Yorubas as well as anti-C and anti-E. The observation was similar in the Igbo and Hausa groups. There is a need to determine these antibodies and monitor their titre in pregnant women to manage or prevent the morbidity and mortality associated with HDFN during routine antenatal care.
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Isoanticuerpos , Mujeres Embarazadas , Embarazo , Recién Nacido , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Prevalencia , Nigeria/epidemiología , Universidades , Hospitales de Enseñanza , FetoRESUMEN
BACKGROUND: Transfusion-dependent thalassemia patients are at high risk of transfusion-related complications. Yet, there is scanty data on the frequency of transfusion reactions, particularity alloimmunization among pediatric transfusion-dependent thalassemia patients. In addition, there is no consensus on the prophylactic antigen matching for prevention of alloimmunization or the extent of antigen matching for alloimmunized thalassemia patients. METHODS: We conducted a retrospective study to assess the frequency and specificity of alloimmunization among pediatric transfusion-dependent thalassemia patients receiving ABO, RhD, and K-matched red blood cell units. In addition, we studied the association between patients' characteristics and alloimmunization. The clinical and transfusion records of transfusion-dependent thalassemia patients followed up at our institution between July 2018 and June 2022 were reviewed. RESULTS: Ninety-two transfusion-dependent thalassemia patients having mean age of 13.37 years (SD, 5.56) were included in our study. Eight patients (9%) had developed clinically significant alloantibodies; six patients (6%) developed alloantibody against E antigen while two patients (2%) developed more than one alloantibody. Of alloimmunized patients, five patients had received transfusion outside Canada. Patients' sex, age, having a genotype variant, total number, and duration of transfusion received were not associated with the risk of alloimmunization. The transfusion-recipient's diagnosis of ß-thalassemia, having developed autoantibody, and history of receiving transfusion outside Canada were associated with alloimmunization. CONCLUSION: Blood matching for ABO, RhD, and K antigens resulted in, although not eliminated, lower frequency of alloimmunization than that previously reported among pediatric thalassemia patients. Extending matching to include Rh antigens could further reduce the rate of alloimmunization.