| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
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| 9. |
- Allhorn, Maria, et al.
(författare)
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Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.
- 2002
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Ingår i: Blood. - 1528-0020. ; 99:6, s. 1894-1901
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Tidskriftsartikel (refereegranskat)abstract
- alpha(1)-Microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. alpha(1)-Microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. alpha(1)-Microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA-alpha(1)-microglobulin as well as from free alpha(1)-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t-alpha(1)-microglobulin binds heme and the alpha(1)-microglobulin-heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t-alpha(1)-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that alpha(1)-microglobulin is involved in extracellular heme catabolism. (Blood. 2002;99:1894-1901)
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| 10. |
- Allhorn, Maria, et al.
(författare)
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The IgG specific endoglycosidase EndoS inhibits both cellular and complement mediated autoimmune hemolysis.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:24, s. 5080-5088
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Tidskriftsartikel (refereegranskat)abstract
- EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized RBC. The toxic effects of monocytes stimulated with anti-D-sensitized RBC, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBC and complement mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBC was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC IgG2a monoclonal autoantibody, and complement activation and erythrophagocytosis by Kupffer cells in the liver, were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody mediated destruction of RBC.
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