Blood Group Systems Overview

Blood groups are genetically discrete groups of antigens controlled by a single gene or cluster of two or three closely linked homologous genes. This article will provide an introduction to blood group system categorization and functional roles.

Discovery of Blood Groups

The first blood group was discovered at the beginning of the twentieth century when the Austrian physician Karl Landsteiner mixed sera and red cells of five co-workers. This experiment led him to identify different agglutination patterns that he categorized into three blood groups A, B, O. Following this discovery, transfusions could be successfully performed on a regular basis without fearing major complications of hemolytic reactions threatening the health or even the life of the transfused patient.

Several decades after the discovery of the A,B and O blood groups, the identification of one of the largest blood group systems, the Rh blood group (including over 50 antigens), led to the understanding, and subsequent prevention, of hemolytic disease of the fetus and newborn (HDFN). ABO and Rh blood groups are without doubt the most important blood group systems in transfusion medicine; however, antibodies to many other blood group antigens have also been shown to cause hemolytic reactions and HDFN.

Current ISBT Blood Group Systems and Antigens

The International Society of Blood Transfusion (ISBT) has published their most updated Blood Group System table in July 2023. Three hundred and sixty (360) blood group antigens, inherited and defined serologically by human made antibodies, are identified by an ISBT number* and categorized into one of 45 known blood group systems. Most of the remaining antigens are allocated to:

• Collections, the 200 series, that do not fulfill all requirements for a blood group system
• Low incidence antigens, the 700 series, defined as inherited antigens with an incidence of less than 1% in most populations
• High incidence antigens, the 901 series, defined as inherited antigens with an incidence of over 90% in most populations

Do Blood Group Antigens Have a Functional Role?

Despite a wealth of information on structural features of blood group antigens, surprisingly little is known about their functional roles. However, some red blood cell antigens have been described as:

• Transporters and channels, such as Kidd (urea transporter) and Diego (anion transporter)
• Receptors and adhesion molecules, such as Duffy (chemokine receptor), as well as Indian and Xg (adhesion molecules)
• Enzymes, such as Cartwright, Dombrock (possibly enzymatic), Kell (endopeptidase)
• Structural proteins, such as Lutheran (binds laminin), RHAG (participates in RBC structure)

Molecular Genetic Techniques for Blood Group Antigens

While antigens traditionally are defined serologically by human antibodies, the introduction of molecular genetic techniques into the study of human blood groups has permitted insight into the molecular basis behind allelic differences and blood group polymorphisms. These techniques will continue to not only help patients in need of transfusion, but also in exploring the biological importance of these variants, such as in the battle against infectious diseases.