26 research outputs found

    Allelic Discrimination by TaqMan-PCR for Genotyping of Human Neutrophil Antigens

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    Neutrophil antigens are implicated in a variety of clinical conditions, including neonatal immune neutropenia, transfusion-related acute lung injury, refractoriness to granulocyte transfusions, febrile transfusion reactions, and autoimmune neutropenia. In this report, we describe simultaneous genotyping of human neutrophil antigens (HNA)-1, -3, -4, and -5 using PCR with allele-specific TaqMan probes and end-point fluorescence detection, which is a robust, rapid, and reproducible method, allowing for high-throughput genotyping.</p

    TRALI er en overset alvorlig komplikation i forbindelse med blodtransfusion

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    Transfusion-related acute lung injury (TRALI) is recognized as the most frequent cause of transfusion-related severe morbidity and mortality. TRALI is characterized by post-transfusional respiratory distress, hypoxaemia and radiographic verified lung infiltration, in the absence of sign of circulatory overload. TRALI is predominantly triggered by human leukocyte antigen or human neutrophil antigen (HNA) antibodies from the transfused blood component. Particularly antibodies against the HNA-3a are involved in severe and fatal TRALI cases. The serological investigation is important to trace and exclude blood donors with TRALI antibodies.</p

    Multinational Analysis of Children Transfused With Pathogen Inactivated Platelets

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    BACKGROUND: Pathogen inactivated (PI) platelets are a technological advancement in blood safety; however, the pediatric experience is not well characterized. We studied pediatric patients who received transfusions of PI platelets across several centers and countries to determine if transfusion reaction rates differed when compared with conventional platelets.METHODS: This is a retrospective multisite study conducted during 2 time periods. The study period started at the time each site began using PI platelets on a widespread basis, and the control period was a similar timespan before PI introduction. Suspected acute transfusion reactions were compared.RESULTS: The study included 3839 pediatric patients who were 0 to 18 years of age who received &gt;7930 platelet transfusions, in total, across 4 centers in 3 countries between 2013 and 2019. The age distribution of patients in the study and control period was not significantly different (P = .190). There was not a difference in the percentage of patients who had any type of transfusion reaction between the time periods (1.0% and 1.1%, P = .803). There were fewer patients with mild allergic reactions in the study period compared with the control period (0.2% and 0.7% of patients with reactions, respectively, P = .018).CONCLUSIONS: Pediatric patients have the same rate of acutely suspected transfusion reactions when receiving PI or conventional platelet transfusions. Subgroup analysis found fewer mild allergic reactions in the study period, which was contemporaneous to the addition of using platelet additive solution more broadly. Future studies of PI platelets should include children to better assess transfusion efficacy and hemostatic outcomes.</p

    Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

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    SummaryThird generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour.We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency.Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively.It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.</jats:p

    Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women-2 years of screening experience from Denmark

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    OBJECTIVE: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening.METHODS: Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies.RESULTS: The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%.CONCLUSION: The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance. © 2014 John Wiley &amp; Sons, Ltd.</p

    CD21 deficiency in 2 siblings and frequency of the associated mutation in the Danish population

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    The clinical presentation of CD21 deficiency in 2 siblings caused by a novel mutation in the CD21 gene is reported, and the frequency of this mutation in the Danish population is explored. Successful treatment with IgG replacement in both patients with CD21 deficiency is also reported.</p

    Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients

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    BACKGROUND: Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR, and HLA-DQ alleles with AIN and the association of these genotypes with the presence of autoantibodies.METHODS: Eighty AIN cases with a median age of 13.5 months were included. Controls were healthy unrelated Danish blood donors. Anti-HNA-1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow-GIFT) with phenotyped donor cells for detection of antibody specificity. Molecular determination of HNA genotypes was determined using real-time polymerase chain reaction (q-PCR). High-resolution HLA-DRB1 and HLA-DQB1 were determined by next-generation sequencing.RESULTS: Antibodies against HNA-1a were detected in 51% (n = 41) of AIN patients, and anti-HNA-1b was detected in 3% (n = 2) of cases. In 46% of cases, the antibodies were anti-FcγIIIb-reactive. FCGR3B*01+,*02-,*03- was more common (odds ratio, 6.70; P &lt; .0001), and FCGR3B*01-,*02+,*03- was less common (odds ratio, 0.30; P &lt; .0001) among AIN cases. HNA-1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02-,*03- genotype (odds ratio, 3.86; P &lt; .007). The HLA-DRB1*14 - HLA-DQB1*05:03 haplotype was significantly more common (odds ratio, 7.44; P &lt; .0001) in AIN patients.CONCLUSION: The HLA haplotype HLA-DRB1*14 - DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti-HNA-1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01+,*02-,*03- genotype.</p

    Inherited variation in immune response genes in follicular lymphoma and diffuse large B-cell lymphoma

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    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune mediated survival and proliferation signals from the tumour microenvironment. Inherited genetic variation influences this complex interaction. Eighty-nine studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consistent association exists for variation in the tumour necrosis factor alpha (TNFA) and interleukin-10 loci and DLBCL risk; for DLBCL outcome association with the TNFA locus exists. Variations at chromosome 6p31-32 were associated with FL risk. Most important, individual risk alleles have been shown to interact with each other. We suggest that the pathogenetic impact of polymorphic genes should include gene-gene interaction analysis and should be validated in preclinical model systems of normal B lymphopoiesis and B-cell malignancies. In the future, large cohort studies of interactions and genome-wide association studies are needed to extend the present findings and explore new risk alleles to be studied in preclinical models.</p
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