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Transfusion Medicine (Oxford, England) Feb 2021
Topics: Anemia, Hemolytic, Autoimmune; Humans; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 33570223
DOI: 10.1111/tme.12744 -
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 -
Frontiers in Immunology 2023Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires...
INTRODUCTION
Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Some, but not all, AML patients develop an anti-HLA immune response after multiple transfusions. We therefore hypothesized that different immune activation profiles might be associated with anti-HLA alloimmunization status.
METHODS
We tested this hypothesis, by analyzing CD4+ T lymphocyte (TL) subsets and their immune control molecules in flow cytometry and single-cell multi-omics.
RESULTS
A comparison of immunological status between anti-HLA alloimmunized and non-alloimmunized AML patients identified differences in the phenotype and function of CD4+ TLs. CD4+ TLs from alloimmunized patients displayed features of immune activation, with higher levels of CD40 and OX40 than the cells of healthy donors. However, the most notable differences were observed in non-alloimmunized patients. These patients had lower levels of CD40 and OX40 than alloimmunized patients and higher levels of PD1. Moreover, the Treg compartment of non-alloimmunized patients was larger and more functional than that in alloimmunized patients. These results were supported by a multi-omics analysis of immune response molecules in conventional CD4+ TLs, Tfh circulating cells, and Tregs.
DISCUSSION
Our results thus reveal divergent CD4+ TL characteristics correlated with anti-HLA alloimmunization status in transfused AML patients. These differences, characterizing CD4+ TLs independently of any specific antigen, should be taken into account when considering the immune responses of patients to infections, vaccinations, or transplantations.
Topics: Humans; Blood Platelets; T-Lymphocytes, Helper-Inducer; CD4-Positive T-Lymphocytes; Thrombocytopenia; Anemia, Hemolytic, Autoimmune; CD40 Antigens; Leukemia, Myeloid, Acute
PubMed: 37701444
DOI: 10.3389/fimmu.2023.1165973 -
Transfusion Medicine (Oxford, England) Apr 2023To determine the prevalence of red blood cell (RBC) alloimmunisation and alloantibody specificity in sickle cell disease (SCD) patients in Kisangani, Democratic Republic...
OBJECTIVES
To determine the prevalence of red blood cell (RBC) alloimmunisation and alloantibody specificity in sickle cell disease (SCD) patients in Kisangani, Democratic Republic of Congo (DRC) in comparison with those followed at the Centre Hospitalier Régional (CHR) de la Citadelle of Liège (Belgium).
BACKGROUND
Data regarding RBC alloimmunisation (immune response of the organism to foreign erythrocyte antigens, antigens that lack on its own RBC) in SCD patients are scarce in sub-Saharan Africa.
METHODS
We conducted a multi-site-based cross-sectional study among 125 SCD patients at Kisangani and 136 at the CHR de la Citadelle of Liège. The diagnosis of SCD was confirmed by high-performance liquid chromatography. Alloantibodies were screened using the agglutination technique on gel cards and their specificity determined using 11 and/or 16 cell panels. Statistical analyses were carried out using SPSS.
RESULTS
The prevalence of RBC alloimmunisation was 9.6% among SCD patients in Kisangani versus 22.8% in those of Liège. At Kisangani as well as at Liège, the median age of alloimmunised patients was higher than that of non-alloimmunised patients, 15.5 years (IQR:4.8-19.8) and 24 years (IQR:14-31) versus 10 years (IQR: 6.5-17) and 17 years (IQR:12-24), respectively. The median number of blood units was higher in both Kisangani and Liège immunised patients compared to non-immunised patients, 8 (IQR:5-11) versus 5 (IQR:3-13) and 41(IQR:6-93) versus 6.5(3-37) respectively. At Kisangani (N = 14), the most frequent antibodies were anti-D (28.6%) and anti-C versus anti-E (13.6%), anti-S (13.6%) and anti-Lea (11.4%) at Liège (N = 44).
CONCLUSIONS
These findings stated that alloimmunisation is a common complication in SCD patients in the DRC. In the resource-limited setting of this country, blood transfusion with minimal ABO, D, C and E antigen matching in addition to the use of compatibility test could significantly reduce the incidence of this complication.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Democratic Republic of the Congo; Cross-Sectional Studies; Erythrocytes; Anemia, Sickle Cell; Blood Transfusion; Anemia, Hemolytic, Autoimmune; Isoantibodies; Blood Group Antigens
PubMed: 36377544
DOI: 10.1111/tme.12939 -
Transfusion Clinique Et Biologique :... Feb 2023Human neutrophil antigens (HNAs) and antibodies play an important role in allo- and autoimmunity associated with immune neutropenia and transfusion reactions. The aim of...
OBJECTIVES
Human neutrophil antigens (HNAs) and antibodies play an important role in allo- and autoimmunity associated with immune neutropenia and transfusion reactions. The aim of this study was to determine the HNA-1, -3, -4 and -5 allele and genotype frequencies in the Croatian blood donor population to assess the role of HNA-1, -3, -4, and -5 alleles in the development of neonatal alloimmune neutropenia and antibody-mediated transfusion-related acute lung injury.
MATERIAL AND METHODS
A total of 371 blood samples from unselected healthy blood donors were analyzed. Samples from all 371 donors were genotyped for HNA-1, samples from 160 donors were genotyped for HNA-3, and samples from 142 donors were genotyped for HNA-4 and HNA-5 using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method.
RESULTS
The frequencies of the FCGR3B*01, FCGR3B*02 and FCGR3B*03 HNA-1 alleles were 0.393, 0.607 and 0.022, and of the SLC44A2*01 and SLC44A2*02 HNA-3 alleles 0.781 and 0.219, respectively. The frequencies of the ITGAM*01 and ITGAM*02 HNA-4 alleles were 0.796 and 0.204, and of the ITGAL*01 and ITGAL*02 HNA-5 alleles 0.718 and 0.282, respectively.
CONCLUSION
These are the first results on the HNA allele and genotype frequencies in the Croatian blood donor population. We observed no deviations from previous reports on Caucasian populations. Determination of the HNA antigen frequencies in the population is important to estimate the risk of alloimmunization to HNA, especially the risk of fetal-maternal incompatibility and alloantibody production by transfusion of the HNA incompatible blood components.
Topics: Infant, Newborn; Humans; Alleles; Blood Donors; Gene Frequency; Neutrophils; Clinical Relevance; Croatia; Isoantigens; Genotype; Neutropenia
PubMed: 36243306
DOI: 10.1016/j.tracli.2022.10.001 -
Haematologica Oct 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 increased 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.
Topics: Humans; Mice; Animals; Reticulocytes; Isoantibodies; Blood Donors; Erythrocytes; Risk Factors
PubMed: 37078267
DOI: 10.3324/haematol.2023.282815 -
Transplant Immunology Feb 2022Attaining a fair long-term allograft survival remains a challenge for allogeneic transplantation worldwide. Although the emergence of immunosuppressants has caused... (Review)
Review
Attaining a fair long-term allograft survival remains a challenge for allogeneic transplantation worldwide. Although the emergence of immunosuppressants has caused noticeable progress in the management of immunologic rejection, proper application of these therapeutics and dose adjustments require delicate and real-time monitoring of recipients. Nevertheless, the majority of conventional allograft monitoring approaches are based on organ damage or functional tests that render them unable to predict the rejection events in early time points before the establishment of a functional alloimmune response. On the other hand, biopsy-based methods include invasive practices and are accompanied by serious complications. In recent years, there have been a myriad of attempts on the discovery of reliable and non-invasive approaches for the monitoring of allografts that regarding a close relationship between allografts and hosts' immune system, most of the attempts have been devoted to the studies on the immune response-associated biomarkers. The discovery of gene and protein expression patterns in immune cells along with their phenotypic characterization and secretome analysis as well as tracking the immune responses in allograft tissues and clinical specimens are among the notable attempts taken to discover the non-invasive predictive markers with a proper coincidence to the pathologic condition. Collectively, these studies suggest a list of candidate biomarkers with ideal potentials for early and non-invasive prediction of allograft rejection and shed light on the way towards developing more standardized and reproducible approaches for monitoring the allograft rejection.
Topics: Allografts; Graft Rejection; Histocompatibility; Immunosuppressive Agents; Transplantation, Homologous
PubMed: 34843937
DOI: 10.1016/j.trim.2021.101509 -
Transfusion Medicine (Oxford, England) May 2024Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn...
BACKGROUND
Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn (HDFN). This study aimed to determine the frequencies of alleles, genotypes, and risk of alloimmunisation of clinically significant blood group systems in ethnic northeastern Thais.
METHODS
In total, 345 unrelated, healthy, ethnic northeastern Thais were tested using the in-house PCR-sequence specific primers (PCR-SSP) method for simultaneously genotyping of RHCE, Kell, Duffy, Kidd, Diego and MNS glycophorin hybrids and results confirmed by Sanger sequencing.
RESULTS
In this cohort, the alleles RHCE*C (81.0%) and RHCE*e (84.8%) were more prevalent than RHCE*c (19.0%) and RHCE*E (15.2%). The most common predicted haplotype combinations of the RHCE alleles were C+c-E-e+(RR) (59.4%) followed by the C+c+E+e+ (RR) (20.6%) and C+c+E-e+ (Rr) (11.3%). The KEL*01 allele was not found in this study. The frequencies of FY*01 and FY*02 were 88.3% and 11.7%, respectively. The genotype FY*02/02 was found in four samples (1.2%). The frequencies of JK*01 and JK*02 were 52.5% and 47.5%, respectively. Homozygous JK*02/02 was found in 81 samples (23.5%). The frequencies of DI*01 and DI*02 were 0.6% and 99.4%, respectively. In total, 64 samples (18.6%) were found to carry the MNS glycophorin hybrids.
CONCLUSIONS
Our results indicated a possible high risk of c, E, Fy, Jk, Jk and Mi alloimmunisation in these populations. Moreover, methods established for genotyping clinically significant blood groups in this study can now be utilised in routine clinical application.
PubMed: 38804163
DOI: 10.1111/tme.13055 -
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 -
Frontiers in Immunology 2020Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens,... (Review)
Review
Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil- and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial- and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial- and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.
Topics: Cytokines; Endothelial Cells; Extracellular Vesicles; Immune System; Kidney; Kidney Diseases; Kidney Transplantation; Kidney Tubules; Macrophages; Mesenchymal Stem Cells; Reperfusion Injury; T-Lymphocytes; Transplants
PubMed: 32180768
DOI: 10.3389/fimmu.2020.00074