scholarly journals Inhibition of the Transcription Factor RUNX1 Causes Glycosyltransferase a Repression

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 925-925
Author(s):  
Romy Kronstein-Wiedemann ◽  
Laura Schmidt ◽  
Jörn Lausen ◽  
Erhard Seifried ◽  
Torsten Tonn
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Blood Group ◽  
Receptor Expression ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Hematopoietic Stem ◽  
Blood Group A ◽  
Homozygous Genotype ◽  
Group A

Abstract Background: The ABO blood group system is unequivocally the most important in clinical transfusion medicine. Furthermore ABO is implicated in the development of a number of human diseases. The ABO antigens are not confined to RBCs but are widely expressed in a variety of human cells and tissues. Thus, ABO matching is critical not only in blood transfusion but also in cell, tissue and organ transplantation. The molecular genetic basis of the ABO system has been known since 1990. However, despite extensive investigations about regulation of ABO blood group receptor expression, the mechanism is not fully resolved. Previously we found that miRNAs plays a critical role in regulation of ABO blood group antigen. Numerous miRNAs which were up- or downregulated in RBCs of blood group O and of heterozygous genotypes as compared to homozygous genotype possess potential binding sites in the 3'UTR of several transcription factors, such as SP1 and RUNX1. Here we show that silencing of the transcription factor RUNX1 leads to downregulation of blood group A antigen. Methods: We performed knockdown experiments for RUNX1 by lentiviral gene transfer of shRNA in primary hematopoietic stem cells (HSCs) and analyzed blood group A-antigen expression using different method, including flow cytometry, western blot and qPCR. Result: Knockdown of RUNX1 in HSCs leads to a 10-20% reduction of blood group A positive erythroid cells and a 30-40% reduction of blood group A antigens per cell in differentiated RBCs. Furthermore, microarray analysis showed a significant increase of miR-215-5p and miR-192-5p in RBCs of blood group O as compared to homozygous genotype. RUNX1 is known to be a target gene for these miRNAs. Conclusion: Glycosyltransferase A and B expression is regulated by different miRNAs, via simultaneously targeting of the transcription factors SP1 and Runx1 and glycosyltransferase A and B mRNA. The knowledge of the role of microRNAs and the transcription factors SP1 and RUNX1 in the expression of blood group antigens may be extended to other blood groups (Rhesus, Kell, Duffy) and may open the door for therapeutic interventions in diseases where blood group receptors promote disease pathology. Disclosures No relevant conflicts of interest to declare.

Normal Human Serum Contains Natural Antibodies Reactive With Autologous ABO Blood Group Antigens

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4418-4424 ◽  
Author(s):  
Sergio H. Spalter ◽  
Srini V. Kaveri ◽  
Emmanuelle Bonnin ◽  
Jean-Claude Mani ◽  
Jean-Pierre Cartron ◽  
...  
Keyword(s):  
Human Serum ◽  
Blood Group ◽  
Autologous Blood ◽  
Natural Antibodies ◽  
Normal Human Serum ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Blood Group A ◽  
Group A ◽  
Normal Human

Abstract It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual’s red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that IgM and IgG antibodies reactive with autologous blood group antigens are present in the immunoglobulin fraction of normal human serum. Natural IgG anti-A antibodies purified by affinity chromatography from IgG of individuals of blood group A exhibited an affinity for A trisaccharide antigen in the micromolar range and agglutinated A red cells at sixfold higher concentrations than those required for agglutination with affinity-purified anti-A IgG of individuals of blood group B. Whereas autoantibodies reactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result of complementary interactions between variable regions of antibodies. These observations suggest that tolerance to autologous ABO blood group antigens is dependent on peripheral control of antibody autoreactivity.

Normal Human Serum Contains Natural Antibodies Reactive With Autologous ABO Blood Group Antigens

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4418-4424 ◽  
Author(s):  
Sergio H. Spalter ◽  
Srini V. Kaveri ◽  
Emmanuelle Bonnin ◽  
Jean-Claude Mani ◽  
Jean-Pierre Cartron ◽  
...  
Keyword(s):  
Human Serum ◽  
Blood Group ◽  
Autologous Blood ◽  
Natural Antibodies ◽  
Normal Human Serum ◽  
Abo Blood Group ◽  
Blood Group Antigens ◽  
Blood Group A ◽  
Group A ◽  
Normal Human

It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual’s red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that IgM and IgG antibodies reactive with autologous blood group antigens are present in the immunoglobulin fraction of normal human serum. Natural IgG anti-A antibodies purified by affinity chromatography from IgG of individuals of blood group A exhibited an affinity for A trisaccharide antigen in the micromolar range and agglutinated A red cells at sixfold higher concentrations than those required for agglutination with affinity-purified anti-A IgG of individuals of blood group B. Whereas autoantibodies reactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result of complementary interactions between variable regions of antibodies. These observations suggest that tolerance to autologous ABO blood group antigens is dependent on peripheral control of antibody autoreactivity.

scholarly journals Downregulation of Glycosyltransferase a Expression By miRNA-331-3p Is Mediated By the Inhibition of the Transcription Factor SP1

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1247-1247
Author(s):  
Romy Kronstein-Wiedemann ◽  
Peter Bugert ◽  
Erhard Seifried ◽  
Torsten Tonn
Keyword(s):  
Transcription Factor ◽  
Protein Expression ◽  
Blood Group ◽  
Antigen Expression ◽  
Blood Group Antigen ◽  
Luciferase Reporter ◽  
Hematopoietic Stem ◽  
Blood Group A ◽  
Transcription Factor Sp1 ◽  
Group A

Abstract More than 100 ABO subgroup-related variations were detected in the coding region of glycosyltransferases, which may be causative for a weak blood group antigen A or B expression. Most variation in expression is explained genetically by mutations that reduce transferase activity. However, a substantial number of weak variants have not yet been explained by current methods. We recently postulated a role of miRNA in the regulation of blood group A antigen expression levels. By using different approaches, including gene array analysis, luciferase reporter assay and overexpression of glycosyltransferase specific miRNAs in primary hematopoietic stem cells (HSCs), we found that miR-331-3p directly targets glycosyltransferase A and B mRNA. Now we have been further embarking on the underlying mechanisms of miRNA and glycosyltransferase interactions and show that the effects of miR-331-3p are mediated by inhibition of transcription factor SP1, which is a major regulator of the ABO gene, thereby resulting in downregulation of blood group A antigen expression in A2O individuals by up to 80% and in A1O individuals by up to 50%. Using microRNA target prediction tools we also identified Sp1 as a potential target gene for miR-331-3p. Western blot analyses of glycosyltransferase protein expression showed that overexpression of miR-331 led to a decreased glycosyltransferase and SP1 protein expression. Further approaches with the SP1 inhibitor, mithramycin A, revealed similar results. Analysis of Aw04/O1v genotypes revealed elevated miRNA levels, thus confirming microRNAs as regulators of blood group glycosyltransferase expression. Our findings extend our understanding of blood group regulation in carriers of weak blood group variants. Involvement of miRNAs in the downregulation of ABO blood group antigen expression may also provide an explanation for observed changes of ABO antigen expression in abnormal processes such as tumorigenesis, pregnancy and aging. Furthermore, this pathway may play a role in the regulation of other blood group variants (for instance Rhesus, KELL, amongst others). Disclosures No relevant conflicts of interest to declare.

scholarly journals ABO groups can play a role in susceptibility and severity of COVID-19

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
S. Samra ◽  
M. Habeb ◽  
R. Nafae
Keyword(s):  
Blood Group ◽  
Abo Blood Group ◽  
Infection Group ◽  
Mechanically Ventilated ◽  
Blood Group A ◽  
Group A ◽  
Study Population ◽  
Group B ◽  
The Relationship ◽  
Seriously Ill

Abstract Background A few people infected by the coronavirus become seriously ill, while others show little to no signs of the symptoms, or are asymptomatic. Recent researches are pointing to the fact that the ABO blood group might play an important role in a person’s susceptibility and severity of COVID-19 infection. Aim of the study: try to understand the relationship between ABO groups and COVID-19 (susceptibility and severity). Results A total of (507) patients were included in this study. The study population was divided based on the ABO blood group into types A+, A−, B+, AB, O+, and O−. Blood group A was associated with high susceptibility of infection: group A, 381 (75.1%); and less common in group O, 97 (19.2%), group B, 18 (3.5%), and group AB, 11 (2.2%). The severity of COVID-19 infection was common in non-blood group O where (20 (7.1%), 4 (26.7%), 2 (11%), and 1 (9%) in type A+, A−, B+, and AB, respectively), while in type O 3.1%. And mechanically ventilated patients were 22 (5.9%), 2 (13.4%), 2 (11.1%), and 1 (1%). Mortality was high in blood groups A and B, 16 (4.37%) and 1 (5.5%), respectively, while in blood group O, it was 1%. Conclusion The incidence, severity, and mortality of COVID-19 were common in non-blood group O. While blood group O was protected against COVID-19.

scholarly journals Heterogeneic expression of blood group A and H isoantigens in bladder tumors: association with nuclear volume.

1989 ◽  
Vol 37 (7) ◽  
pp. 1153-1155 ◽  
Author(s):  
T F Orntoft ◽  
K Nielsen
Keyword(s):  
Blood Group ◽  
Transitional Cell ◽  
Antigen Expression ◽  
Nuclear Volume ◽  
Intratumor Heterogeneity ◽  
Blood Group Antigens ◽  
Pathological Grade ◽  
Blood Group A ◽  
Group A ◽  
The Mean

Intratumor heterogeneity is a major problem in immunodiagnosis and treatment of carcinomas. To elucidate the well-known heterogeneity in transitional-cell carcinomas of the ability to express blood group ABO isoantigens, a stereological estimate of the mean nuclear volume in areas expressing blood group antigens was compared to the estimate from areas of identical pathological grade at which antigen expression was deleted. Four microscopic fields were examined from antigen-positive and four from antigen-negative areas in sections from 21 blood group O and 20 blood group A individuals. The sections were stained before examination by an indirect peroxidase method using monoclonal anti-H and anti-A antibodies. The mean nuclear volume increased, as expected, with increasing pathological grade. In blood group O individuals the mean nuclear volume was 241.5 microns 3 in antigen-positive areas and 338.2 microns 3 in antigen-negative areas (2p less than 0.0005) of identical pathological grade. In group A individuals the mean nuclear volume was 217.1 microns 3 in positive areas and 351.1 microns 3 in corresponding negative areas (2p less than 0.0025). The variation in volume parameter was essentially caused by a true variation between tumors (greater than 82%). The results indicate a complex biological mechanism associated with the cellular ability to express blood group antigens.

scholarly journals The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to MaternalABOGenotypes

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Maria Therese Ahlen ◽  
Anne Husebekk ◽  
Mette Kjær Killie ◽  
Jens Kjeldsen-Kragh ◽  
Martin L. Olsson ◽  
...  
Keyword(s):  
Relative Risk ◽  
Pregnant Women ◽  
Blood Group ◽  
Lower Risk ◽  
Abo Blood Group ◽  
Severe Thrombocytopenia ◽  
Blood Group A ◽  
Group A ◽  
Alloimmune Thrombocytopenia ◽  
Design And Methods

Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies.Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated.Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75).Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternalABOtypes, and this study indicates that the observation is due to genetic properties on the maternal side.

scholarly journals Association of ABO blood group with fracture pattern and mortality in hip fracture patients

2014 ◽  
Vol 96 (6) ◽  
pp. 442-445 ◽  
Author(s):  
CE Uzoigwe ◽  
RP Smith ◽  
A Khan ◽  
D Aghedo ◽  
M Venkatesan
Keyword(s):  
Hip Fracture ◽  
Blood Group ◽  
Femoral Fracture ◽  
Intertrochanteric Fracture ◽  
Proximal Femoral Fracture ◽  
Fracture Pattern ◽  
Abo Blood Group ◽  
Blood Group A ◽  
Fracture Configuration ◽  
Group A

Introduction The mechanism of falling has been proposed as the exclusive explanation for hip fracture pattern. Evidence exists that other genetic factors also influence proximal femoral fracture configuration. The ABO blood group serotype has been associated with other pathologies but any role in hip fracture has yet to be definitively characterised. Methods Our National Hip Fracture Database was interrogated over a four-year period. All patients had their blood group retrieved, and this was compared with hip fracture pattern and mortality rates. Confounding factors were accounted for using logistic regression and the Cox proportional hazards model. Results A total of 2,987 consecutive patients presented to our institution. Those with blood group A were significantly more likely to sustain intracapsular fractures than ‘non-A’ individuals (p=0.009). The blood group distribution of patients with intracapsular fractures was identical to that of the national population of England. However, blood group A was less common in patients with intertrochanteric fractures than in the general population (p=0.0002). Even after correction for age and sex, blood group A was associated with a decrease in the odds of suffering an intertrochanteric fracture to 80% (p=0.002). Blood group A had inferior survivorship correcting for age, sex and hip fracture pattern (hazard ratio: 1.14, p=0.035). This may be due to associated increased prevalence of co-morbid disease in this cohort. Conclusions Blood group is an independent predictor of hip fracture pattern, with group A patients more likely to sustain an intracapsular fracture and non-A individuals more likely to sustain an intertrochanteric fracture. The determinants of fracture pattern are likely to be related to complex interactions at a molecular level based on genetic susceptibility. The mechanism of fall may not be the only aetiological determinant of proximal femoral fracture configuration.

scholarly journals Blood Group A Antigen Is a Coreceptor inPlasmodium falciparum Rosetting

2000 ◽  
Vol 68 (5) ◽  
pp. 2971-2975 ◽  
Author(s):  
Antonio Barragan ◽  
Peter G. Kremsner ◽  
Mats Wahlgren ◽  
Johan Carlson
Keyword(s):  
Blood Group ◽  
Blood Cells ◽  
Malaria Parasite ◽  
General Feature ◽  
Enzymatic Digestion ◽  
Clinical Isolates ◽  
Rosette Formation ◽  
Blood Group Antigens ◽  
Blood Group A ◽  
Group A

ABSTRACT The malaria parasite Plasmodium falciparum utilizes molecules present on the surface of uninfected red blood cells (RBC) for rosette formation, and a dependency on ABO antigens has been previously shown. In this study, the antirosetting effect of immune sera was related to the blood group of the infected human host. Sera from malaria-immune blood group A (or B) individuals were less prone to disrupt rosettes from clinical isolates of blood group A (or B) patients than to disrupt rosettes from isolates of blood group O patients. All fresh clinical isolates and laboratory strains exhibited distinct ABO blood group preferences, indicating that utilization of blood group antigens is a general feature of P. falciparumrosetting. Soluble A antigen strongly inhibited rosette formation when the parasite was cultivated in A RBC, while inhibition by glycosaminoglycans decreased. Furthermore, a soluble A antigen conjugate bound to the cell surface of parasitized RBC. Selective enzymatic digestion of blood group A antigen from the uninfected RBC surfaces totally abolished the preference of the parasite to form rosettes with these RBC, but rosettes could still form. Altogether, present data suggest an important role for A and B antigens as coreceptors in P. falciparum rosetting.

scholarly journals Frequency of ABO and Rhesus blood groups in Saudi healthy blood donors versus non-Saudi in a retrospective study in Makkah City

2021 ◽  
Vol 1 (1) ◽  
pp. 2-13
Author(s):  
Amal z. Moustafa ◽  
Mohammed S. Aldosari ◽  
Talat A. AL-Bukhari ◽  
Younis A. Allohibi ◽  
Shirin H . Teama ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Blood Group ◽  
Blood Donors ◽  
Blood Groups ◽  
Abo Blood Group ◽  
Sri Lankan ◽  
Blood Storage ◽  
Blood Group A ◽  
Group A ◽  
Makkah City

Purpose: to assess the frequency of ABO and Rh blood groups among Saudi and non-Saudi healthy blood donors and to compare between them. Methods: A retrospective study was conducted; in Makkah City, Saudi Arabia. It included 15,365 participants of 44 nationalities who have attended the blood bank of King Abdul Aziz Hospital. The collected data were age, sex, nationality, ABO, and Rhesus blood groups.  Results: 46.8 % of the participants were O, 28.8 % A, 19.5 % B, and 4.9% AB. The nationalities with a higher frequency of blood group O were Saudi, Mauritanian, Yemeni, Thai, Malian, Sudanese, Jordanian, Indian, Moroccan, Somali, Malaysian, Indonesian, Myanmar, Nigerian, Pakistani, Bangladeshi, Algerian, Djibouti, Burkinabe, Eritrean, Ghanaian, Bahraini, Bosnian, Canadian, Gambian, Iraqi, and Sri Lankan. Those with a higher frequency of blood group A were Turkish, Palestinian, Syrian, Lebanese, Egyptian, Afghan, Chadian, French, Tunisian, Cameroonian, Ethiopian, and British.  Those with a higher frequency of B were Nigerien, American, Nepalese, and two nationalities with higher AB frequency Filipino and Chinese. 91.6 % of all populations were Rh-positive, and 8.4% were Rh-negative. The Saudi participants were like some nationalities and differed from others. Conclusion:  In Makkah city, the higher frequency of ABO blood group in Saudi and non -Saudi people is O followed by A, then B, and AB.  The Rh-positive is predominant, and 8.4% of the participants are negative. The ABO and Rh blood groups' identifications are essential for providing suitable blood storage for individuals in need.

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