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| 2. |
- Babiker-Mohamed, H, et al.
(författare)
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Alpha 1-microglobulin is mitogenic to human peripheral blood lymphocytes. Regulation by both enhancing and suppressive serum factors
- 1990
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Ingår i: Immunobiology. - 1878-3279. ; 180:2-3, s. 221-234
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Tidskriftsartikel (refereegranskat)abstract
- Human alpha 1-microglobulin (alpha 1-m), a 26 kilodalton serum glycoprotein, was found to exert mitogenic effects on human peripheral blood lymphocytes (PBL) in serum-free medium. Purified T cells, but not B cells, responded with proliferation to alpha 1-m, but only in the presence of monocytes. The mitogenic activity could be partially neutralized by a mouse monoclonal antibody against alpha 1-m. The mitogenicity was species-specific, since alpha 1-m homologues from rats, guinea pigs and rabbits had no effect on human PBL. In a previous study, no effect of alpha 1-m was seen on PBL in the presence of 20% serum, and, therefore, we studied the influence of different concentrations of serum on the alpha 1-m-induced mitogenicity. Thus, human serum enhanced the mitogenic effects of alpha 1-m on human PBL at 1% concentration (v/v) and suppressed the effects at 10%. The suppressing effect of serum at 10%, but not the enhancing effect at 1%, seemed to be conserved among several species. To test the effect of serum proteins of different molecular sizes, human autologous serum was separated by gel chromatography on Sephadex G-200 into four fractions. Fractions 1 and 2 (roughly containing proteins larger than 100 kilodaltons) suppressed the mitogenic effects of alpha 1-m, while fractions 3 and 4 enhanced the stimulation by alpha 1-m, at 0.5% and concentrations above. It is concluded that the mitogenic effect of alpha 1-m on lymphocytes is regulated by several serum factors, both enhancing and suppressive, that does not have any proliferative effect of their own. It can be speculated that the balance between enhancing and suppressing co-factors in the blood determines the degree of the stimulation of lymphocytes by alpha 1-m. This is compatible with an immunomodulatory role for alpha 1-m, in spite of its relatively constant plasma levels in health and disease.
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| 3. |
- 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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| 4. |
- Goel, Suchi, et al.
(författare)
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RIFINs are adhesins implicated in severe Plasmodium falciparum malaria
- 2015
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:4, s. 314-317
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Tidskriftsartikel (refereegranskat)abstract
- Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), bind to RBCs-preferentially of blood group A-to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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| 5. |
- Moslemi, Camous, et al.
(författare)
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A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19
- 2023
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 63:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. Study design and methods: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. Results: The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p <.001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p <.001, 1.17 CI[1.14–1.2] p <.001, and 1.2 CI[1.14–1.26] p <.001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. Discussion: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.
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| 6. |
- Nylander, Anja, et al.
(författare)
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An investigation of the interaction between red blood cells and Streptococcus pyogenes
- 2010
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Konferensbidrag (refereegranskat)abstract
- Blood group antigens may be used as receptors by pathogens when infecting their hosts. Different blood groups therefore can be disease susceptibility factors. Thus, pathogens may have exerted a selection pressure on the evolution of blood group diversity. One aim of our study was to identify red blood cell (RBC) membrane structures that are bound by the common human pathogen. Streptococcus pyogenes, responsible for conditions like pharyngitis, Scarlet fever, necrotizing fasciitis and rheumatic heart disease. We also wanted to explore any differences in the ability of S. pyogenes to agglutinate RBC of different ABO groups and of selected null blood group phenotypes.Solubilized RBC membranes were incubated with different strains of S. pyogenes. RBC proteins that bound to bacteria were eluted and separated by SDS-PAGE. In our initial studies, a strong band at ~58 kDa and a weaker band at ~28 kDa were visualized by Coomassie staining. Subsequent analysis by mass spectrometry and Western blotting revealed the bands to correspond to IgG heavy and light chains. The IgG-related bands were strongest for bacterial strains expressing both protein H and M protein, surface structures known to bind IgG, while weaker or no bands were detected in those strains lacking one or both proteins. Results from subsequent experiments indicated that the interaction between S. pyogenes and RBCs was not limited to IgG, but that a number of other RBC membrane structures appear to bind specifically to S. pyogenes. Those proteins are currently being analysed by mass spectrometry.In agglutination studies of S. pyogenes and RBCs, either sensitised with IgG or stripped of IgG we confirmed that IgG has a role in the binding of RBCs by S. pyogenes. We observed no difference in the ability of S. pyogenes to agglutinate RBCs of different ABO groups, indicating that the ABO-specific differences in RBC surface oligosaccharides are not recognized. When we tested a panel of RBCs with rare null phenotypes we found that cells of the Helgeson phenotype, expressing very low levels of the Knops antigens on complement receptor 1 (CR1), agglutinated more weakly than other common and rare RBCs tested.We are still puzzled by the fact that the hemagglutination is stronger for S. pyogenes strains lacking the M-protein, known to bind both complement and IgG on the surface of the bacteria. Our hypothesis is that there might be some repulsive force acting between the M-protein and surface of RBC, making the interaction stronger when the M-protein is missing. This is supported by agglutination studies with papain-treated RBCs, where the negative charge is reduced.IgG is known to bind senescent cell antigens on erythroid band 3 and thus the amount of IgG increases on the RBC surface as it ages. We speculated that binding to IgG on the RBC surface by S. pyogenes could be a way to selectively target aged RBCs, possibly to acquire heme as a source of iron. Attempts to separate RBCs according to age were made on density gradients, followed by agglutination studies of the different fractions. Our initial results did not demonstrate any conclusive differences. Our data indicate that interactions between S. pyogenes and RBC are mediated at least through IgG and CR1 on the RBC surface. The clinical importance awaits exploration but may be relevant in the identification of resistance factors to infections among humans, and could thus lead to the development of alternative ways to treat infections caused by S. pyogenes.
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| 7. |
- Stenfelt, Linn, et al.
(författare)
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Glycoproteomic and Phenotypic Elucidation of B4GALNT2 Expression Variants in the SID Histo-Blood Group System
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The Sd(a) histo-blood group antigen (GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta-R) is implicated in various infections and constitutes a potential biomarker for colon cancer. Sd(a-) individuals (2-4% of Europeans) may produce anti-Sd(a), which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sd(a++)/Cad phenotype are involved. We previously reported the association of B4GALNT2 mutations with Sd(a-), which established the SID blood-group system. The present study provides causal proof underpinning this correlation. Sd(a-) HEK293 cells were transfected with different B4GALNT2 constructs and evaluated by immunostaining and glycoproteomics. The predominant SIDnull candidate allele with rs7224888:T>C (p.Cys406Arg) abolished Sd(a) synthesis, while this antigen was detectable as N- or O-glycans on glycoproteins following transfection of wildtype B4GALNT2. Surprisingly, two rare missense variants, rs148441237:A>G and rs61743617:C>T, found in a Sd(a-) compound heterozygote, gave results similar to wildtype. To elucidate on whether Sd(a++)/Cad also depends on B4GALNT2 alterations, this gene was sequenced in five individuals. No Cad-specific changes were identified, but a detailed erythroid Cad glycoprotein profile was obtained, especially for glycophorin-A (GLPA) O-glycosylation, equilibrative nucleoside transporter 1 (S29A1) O-glycosylation, and band 3 anion transport protein (B3AT) N-glycosylation. In conclusion, the p.Cys406Arg beta 4GalNAc-T2 variant causes Sd(a)-deficiency in humans, while the enigmatic Cad phenotype remains unresolved, albeit further characterized.
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| 8. |
- Storry, Jill, et al.
(författare)
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Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 537-U109
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Tidskriftsartikel (refereegranskat)abstract
- The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that similar to 1 of 17 Swedish blood donors is a heterozygous deletion carrier and similar to 1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system.
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| 9. |
- Westman, Julia, et al.
(författare)
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Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:30, s. 18505-18518
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Tidskriftsartikel (refereegranskat)abstract
- The x(2) glycosphingolipid is expressed on erythrocytes from individuals of all common blood group phenotypes and elevated on cells of the rare P/P1/P-k-negative p blood group phenotype. Globoside or P antigen is synthesized by UDP-N-acetylgalactosamine: globotriaosyl-ceramide 3-beta-N-acetylgalactosaminyl-transferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAc beta 3Gal, as x(2). We encountered a patient with mutations in B3GALNT1 causing the rare P-deficient P-1(k) phenotype and whose pretransfusion plasma was unexpectedly incompatible with p erythrocytes. The same phenomenon was also noted in seven other unrelated P-deficient individuals. Thin-layer chromatography, mass spectrometry, and flow cytometry were used to show that the naturally occurring antibodies made by p individuals recognize x(2) and sialylated forms of x(2), whereas x(2) is lacking on P-deficient erythrocytes. Overexpression of B3GALNT1 resulted in synthesis of both P and x(2). Knockdown experiments with siRNA against B3GALNT1 diminished x(2) levels. We conclude that x(2) fulfills blood group criteria and is synthesized by UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase. Based on this linkage, we proposed that x(2) joins P in the GLOB blood group system (ISBT 028) and is renamed PX2 (GLOB2). Thus, in the absence of a functional P synthase, neither P nor PX2 are formed. As a consequence, naturally occurring anti-P and anti-PX2 can be made. Until the clinical significance of anti-PX2 is known, we also recommend that rare P-1(k) or P-2(k) erythrocyte units are preferentially selected for transfusion to P-k patients because p erythrocytes may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels.
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