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Expresser phenotype determines ABO(H) blood group antigen loading on platelets and von Willebrand factor

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posted on 11.06.2021, 16:31 by Diarmaid O’Donghaile, P Vincent Jenkins, Rachel T McGrath, Lisa Preston, Stephen P Field, Soracha Enright Ward, Jamie O'Sullivan, James O'Donnell
ABO blood group is associated with cardiovascular disease, with significantly lower risk in blood group O individuals. ABO(H) blood group determinants are expressed on different glycoproteins on platelet surfaces. In addition, ABO(H) structures are also present on VWF glycans. These ABO(H) carbohydrates influence both platelet and VWF function. Previous studies have reported that approximately 5–10% of normal blood donors express abnormally high or low levels of A or B blood group antigens on their platelet surfaces (high expresser phenotype, HXP or low expresser phenotype, LXP respectively). In this study, the biological effects of the ABO Expresser phenotype were investigated. ABO(H) expression on platelets and plasma VWF was studied in a series of 541 healthy blood donors. Overall, 5.6% of our study cohort were classified as HXP, whilst 4.4% satisfied criteria for LXP. We demonstrate that genotype at the ABO blood group locus plays a critical role in modulating the platelet HXP phenotype. In particular, A A genotype is a major determinant of ABO high-expresser trait. Our data further show that ABH loading on VWF is also affected by ABO expresser phenotype. Consequently, A antigen expression on VWF was significantly elevated in HXP individuals and moderately reduced in LXP subjects (P < 0.05). Collectively, these findings suggest that ABO expresser phenotype influences primary hemostasis though several different pathways. Further studies will be required to define whether inter-individual variations in ABO(H) expression on platelets and/or VWF (particularly HXP and LXP) impact upon risk for cardiovascular disease. 1 1

Funding

NIH for the Zimmerman Program (HL081588)

Science Foundation Ireland Principal Investigator Award (11/PI/1066)

Health Research Board Investigator Lead Project Award (ILP-POR-2017-008)

National Children’s Research Centre Project Award (C/18/1)

Irish Blood Transfusion Service

Health and Care Research Wales CRT award 2016-05

History

Comments

The original article is available at https://www.nature.com

Published Citation

O'Donghaile D, Jenkins PV, McGrath RT, Preston L, Field SP, Ward SE, O'Sullivan JM, O'Donnell JS. Expresser phenotype determines ABO(H) blood group antigen loading on platelets and von Willebrand factor. Sci Rep. 2020;10(1):18366.

Publication Date

27 October 2020

PubMed ID

33110150

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Health Professions Education
  • Vascular Biology
  • Immunity, Infection and Inflammation
  • Cancer

Publisher

Nature Publishing Group

Version

  • Published Version (Version of Record)