ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies
Ryan Philip Jajosky,
Shang-Chuen Wu,
Leon Zheng,
Audrey N. Jajosky,
Philip G. Jajosky,
Cassandra D. Josephson,
Marie A. Hollenhorst,
Robert Sackstein,
Richard D. Cummings,
Connie M. Arthur,
Sean R. Stowell
Affiliations
Ryan Philip Jajosky
Joint Program in Transfusion Medicine, Brigham and Women’s Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Biconcavity Inc, Lilburn, GA, USA
Shang-Chuen Wu
Joint Program in Transfusion Medicine, Brigham and Women’s Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Leon Zheng
Joint Program in Transfusion Medicine, Brigham and Women’s Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Audrey N. Jajosky
University of Rochester Medical Center, Department of Pathology and Laboratory Medicine, West Henrietta, NY, USA
Philip G. Jajosky
Biconcavity Inc, Lilburn, GA, USA
Cassandra D. Josephson
Cancer and Blood Disorders Institute and Blood Bank/Transfusion Medicine Division, Johns Hopkins All Children’s Hospital, St. Petersburg, FL, USA; Departments of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Marie A. Hollenhorst
Department of Pathology and Department of Medicine, Stanford University, Stanford, CA, USA
Robert Sackstein
Translational Glycobiology Institute, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
Richard D. Cummings
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Connie M. Arthur
Joint Program in Transfusion Medicine, Brigham and Women’s Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Sean R. Stowell
Joint Program in Transfusion Medicine, Brigham and Women’s Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Corresponding author
Summary: Enzymes catalyze biochemical reactions and play critical roles in human health and disease. Enzyme variants and deficiencies can lead to variable expression of glycans, which can affect physiology, influence predilection for disease, and/or directly contribute to disease pathogenesis. Although certain well-characterized enzyme deficiencies result in overt disease, some of the most common enzyme deficiencies in humans form the basis of blood groups. These carbohydrate blood groups impact fundamental areas of clinical medicine, including the risk of infection and severity of infectious disease, bleeding risk, transfusion medicine, and tissue/organ transplantation. In this review, we examine the enzymes responsible for carbohydrate-based blood group antigen biosynthesis and their expression within the human population. We also consider the evolutionary selective pressures, e.g. malaria, that may account for the variation in carbohydrate structures and the implications of this biology for human disease.
