| 1. |
- Moslemi, Camous, et al.
(författare)
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Genetic prediction of 33 blood group phenotypes using an existing genotype dataset
- 2023
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Ingår i: Transfusion. - 0041-1132. ; 63:12, s. 2297-2310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. Study Design and Methods: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. Results: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa/Cob, Doa/Dob, E/e, Jka/Jkb, Kna/Knb, Kpa/Kpb, M/N, S/s, Sda, Se, and Yta/Ytb, while some performed slightly worse: Fya/Fyb, K/k, Lua/Lub, and Vel ~99%–98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). Discussion: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.
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| 2. |
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| 3. |
- Kelemu, Tsehayneh, et al.
(författare)
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Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:16
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia (PE) is a human specific syndrome with unknown etiology causing maternal and fetal morbidities and mortalities. In PE, maternal inflammatory responses are more exaggerated if the fetus is male than female. Other pregnancy complications such as spontaneous abortions are also more common if the fetus is male. Recent transcriptome findings showed an increased expression of CD99 in erythroid cells from male cord blood in PE. The single nucleotide polymorphism (SNP) rs311103, located in a GATA-binding site in a regulatory region on the X/Y chromosomes, governs a coordinated expression of the Xg blood group members CD99 and Xga in hematopoietic cells in a sex-dependent fashion. The rs311103C disrupts the GATA-binding site, resulting in decreased CD99 expression. We aimed to investigate the association between PE and the allele frequency of rs311103 in pregnancies in a fetal sex-dependent fashion. In a case-controlled study, we included 241 pregnant women, i.e., 105 PE cases and 136 normotensive controls. A SNP allelic discrimination analysis was performed on DNA from maternal venous blood and fetal cord blood by qPCR. A statistically significant association was observed between rs311103 allele frequency and PE in mothers carrying male fetuses. Therefore, the rs311103 genotype may play a role in the pathogenesis of PE in a fetal sex-specific manner.
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| 4. |
- Kristiansson, Amanda, et al.
(författare)
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Human radical scavenger α1-microglobulin protects against hemolysis in vitro and α1-microglobulin knockout mice exhibit a macrocytic anemia phenotype
- 2021
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849. ; 162
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Tidskriftsartikel (refereegranskat)abstract
- During red blood cell (RBC) lysis hemoglobin and heme leak out of the cells and cause damage to the endothelium and nearby tissue. Protective mechanisms exist; however, these systems are not sufficient in diseases with increased extravascular hemolysis e.g. hemolytic anemia. α1-microglobulin (A1M) is a ubiquitous reductase and radical- and heme-binding protein with antioxidation properties. Although present in the circulation in micromolar concentrations, its function in blood is unclear. Here, we show that A1M provides RBC stability. A1M-/- mice display abnormal RBC morphology, reminiscent of macrocytic anemia conditions, i.e. fewer, larger and more heterogeneous cells. Recombinant human A1M (rA1M) reduced in vitro hemolysis of murine RBC against spontaneous, osmotic and heme-induced stress. Moreover, A1M is taken up by human RBCs both in vitro and in vivo. Similarly, rA1M also protected human RBCs against in vitro spontaneous, osmotic, heme- and radical-induced hemolysis as shown by significantly reduced leakage of hemoglobin and LDH. Addition of rA1M resulted in decreased hemolysis compared to addition of the heme-binding protein hemopexin and the radical-scavenging and reducing agents ascorbic acid and Trolox (vitamin E). Furthermore, rA1M significantly reduced spontaneous and heme-induced fetal RBC cell death. Addition of A1M to human whole blood resulted in a significant reduction of hemolysis, whereas removal of A1M from whole blood resulted in increased hemolysis. We conclude that A1M has a protective function in reducing hemolysis which is neither specific to the origin of hemolytic insult, nor species specific.
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| 5. |
- Kristiansson, Amanda, et al.
(författare)
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The Role of α1-Microglobulin (A1M) in Erythropoiesis and Erythrocyte Homeostasis-Therapeutic Opportunities in Hemolytic Conditions
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:19, s. 1-21
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Forskningsöversikt (refereegranskat)abstract
- α1-microglobulin (A1M) is a small protein present in vertebrates including humans. It has several physiologically relevant properties, including binding of heme and radicals as well as enzymatic reduction, that are used in the protection of cells and tissue. Research has revealed that A1M can ameliorate heme and ROS-induced injuries in cell cultures, organs, explants and animal models. Recently, it was shown that A1M could reduce hemolysis in vitro, observed with several different types of insults and sources of RBCs. In addition, in a recently published study, it was observed that mice lacking A1M (A1M-KO) developed a macrocytic anemia phenotype. Altogether, this suggests that A1M may have a role in RBC development, stability and turnover. This opens up the possibility of utilizing A1M for therapeutic purposes in pathological conditions involving erythropoietic and hemolytic abnormalities. Here, we provide an overview of A1M and its potential therapeutic effect in the context of the following erythropoietic and hemolytic conditions: Diamond-Blackfan anemia (DBA), 5q-minus myelodysplastic syndrome (5q-MDS), blood transfusions (including storage), intraventricular hemorrhage (IVH), preeclampsia (PE) and atherosclerosis.
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| 6. |
- Lee, Yan Quan, et al.
(författare)
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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti-Xga production
- 2019
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 59:5, s. 1843-1849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .STUDY DESIGN AND METHODS: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.RESULTS: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence.CONCLUSION: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xgnull phenotype. This deletion was found in 10 of 11 anti-Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored.
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| 7. |
- Svensson, Lola, 1948, et al.
(författare)
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Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:8, s. 1459-68
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Tidskriftsartikel (refereegranskat)abstract
- Abstract In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with α3-N-acetylgalactosamine and can be utilized by pathogens as a host receptor in many mammals. However, primates including humans lack Fs synthase activity and have naturally-occurring Fs antibodies in plasma. We investigated individuals with the enigmatic ABO subgroup Apae and found them to be homozygous for common O alleles. Their erythrocytes had no A antigens but instead expressed Fs glycolipids. The unexpected Fs antigen was confirmed in structural, serological and flowcytometric studies. The Fs synthase gene, GBGT1, in Apae individuals encoded an arginine to glutamine change at residue 296. Gln296 is present in lower mammals whereas Arg296 was found in six other primates, >250 blood donors and Apae family relatives without the Apae phenotype. Transfection experiments and molecular modelling showed that 296Gln reactivates the human Fs synthase. Uropathogenic E.coli containing prsG-adhesin-encoding plasmids agglutinated Apae but not group O cells, suggesting biological implications. Predictive tests for intravascular hemolysis with crossmatch-incompatible sera indicated complement-mediated destruction of Fspositive erythrocytes. Taken together, we provide the first conclusive description of Fs expression in normal human hematopoietic tissue and the basis of a new histo-blood group system in man, FORS.
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| 8. |
- Alattar, Abdul Ghani, et al.
(författare)
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Evidence that CD36 is expressed on red blood cells and constitutes a novel blood group system of clinical importance
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Ingår i: Vox Sanguinis. - 1423-0410. ; , s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Polymorphic molecules expressed on the surface of certain blood cells are traditionally categorized as blood groups and human platelet or neutrophil antigens. CD36 is widely considered a platelet antigen (Nak a ) and anti-CD36 can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) in CD36-negative pregnant women. CD36 is used as a marker of differentiation in early erythroid culture. During the experimental culture of CD34+ cells from random blood donors, we observed that one individual lacked CD36. We sought to investigate this observation further and determine if CD36 fulfils the International Society of Blood Transfusion criteria for becoming a blood group. MATERIALS AND METHODS: Surface markers were monitored by flow cytometry on developing cells during the erythroid culture of CD34+ cells. Genetic and flow cytometric analyses on peripheral blood cells were performed. Proteomic datasets were analysed, and clinical case reports involving anti-CD36 and foetal anaemia were scrutinized.RESULTS: Sequencing of CD36-cDNA identified homozygosity for c.1133G>T/p.Gly378Val in the CD36-negative donor. The minor allele frequency of rs146027667:T is 0.1% globally and results in abolished CD36 expression. CD36 has been considered absent from mature red blood cells (RBCs); however, we detected CD36 expression on RBCs and reticulocytes from 20 blood donors. By mining reticulocyte and RBC datasets, we found evidence for CD36-derived peptides enriched in the membrane fractions. Finally, our literature review revealed severe cases of foetal anaemia attributed to anti-CD36.CONCLUSIONS: Based on these findings, we conclude that CD36 fulfils the criteria for becoming a new blood group system and that anti-CD36 is implicated not only in FNAIT but also foetal anaemia.
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