Blood Group Systems and Antigen Detection

Blood group systems are families of inherited antigens carried on the red-cell membrane, defined and named by the International Society of Blood Transfusion according to the genes that encode them. Antigen detection is the laboratory process — by serologic typing and, increasingly, molecular genotyping — of determining which antigens a person's red cells carry. Together they form the foundation on which compatible transfusion is built, the ABO and Rh systems being the most clinically important.

Definition

A blood group system is a set of one or more red-cell antigens controlled by a single gene or by closely linked homologous genes; antigen detection is the determination of an individual's antigen profile by serologic or molecular methods.

Scope

This topic covers what defines a blood group system, the major systems (ABO, Rh, Kell, Duffy, Kidd, MNS and others), the structural and genetic basis of red-cell antigens, and how antigens are detected by forward and reverse typing and by genotyping. It is a reference and educational account; it does not give transfusion-selection protocols or clinical instructions.

Core questions

• What criteria make a set of red-cell antigens an ISBT-recognised blood group system?
• Which antigens does an individual's red cells express?
• How do ABO and RhD typing differ in technique and clinical weight?
• When does molecular genotyping add information that serology cannot?

Key concepts

• Blood group system (ISBT-defined)
• ABO system and naturally occurring antibodies
• Rh system and the D antigen
• Kell, Duffy, Kidd, MNS systems
• Forward (cell) and reverse (serum) typing
• Red-cell genotyping
• Antigen immunogenicity
• Phenotype versus genotype

Mechanisms

Blood group antigens are carbohydrate structures (as in ABO) or polymorphic membrane proteins (as in Rh, Kell, Duffy, and Kidd) whose presence is genetically determined. The ISBT classifies an antigen into a system when the gene controlling it is identified and distinct, giving each system a number and each antigen a designation (Storry et al., 2013). Serologic typing detects antigens by agglutination with known antibodies (forward typing) and confirms ABO status by testing serum against known cells (reverse typing); molecular genotyping infers antigen expression from the underlying alleles, which is valuable when recent transfusion, a positive direct antiglobulin test, or rare phenotypes confound serology. The Rh antigens arise from the RhD and RhCE proteins, and the structural complexity of the Rh complex underlies both its strong immunogenicity and its many variants (Westhoff, 2007; Reid & Lomas-Francis, 2004).

Clinical relevance

Accurate antigen typing is the prerequisite for selecting compatible blood and for anticipating alloimmunisation, particularly for the highly immunogenic D antigen and for patients who are chronically transfused. As a reference topic it describes how typing is performed and interpreted; it does not prescribe which units to transfuse to a given patient, a decision that rests with the treating team (Carson et al., 2017).

Epidemiology

More than forty blood group systems carrying hundreds of antigens are now recognised by the ISBT, but the ABO and Rh systems dominate routine practice because of the frequency and clinical consequence of their antibodies. The prevalence of individual antigens varies markedly between populations, which is relevant to finding compatible units for alloimmunised and chronically transfused patients (Storry et al., 2013; Reid & Lomas-Francis, 2004).

History

Karl Landsteiner's discovery of the ABO groups in 1901 founded the field and earned a Nobel Prize, making safe transfusion possible for the first time. The identification of the Rh system in the 1940s explained haemolytic disease of the fetus and newborn and added the most immunogenic non-ABO antigen to routine practice. The International Society of Blood Transfusion later established a formal, gene-based system of nomenclature, and the cataloguing of antigens by Reid and Lomas-Francis, together with the molecular characterisation of the Rh complex, brought order to an expanding map of red-cell antigens (Storry et al., 2013; Westhoff, 2007).

Key figures

• Karl Landsteiner
• Jill Storry
• Connie Westhoff
• Marion Reid

Seminal works

• storry-2013
• westhoff-2007
• reid-2004

Frequently asked questions

What makes a set of antigens a blood group 'system'?

The ISBT designates a blood group system when the antigens are controlled by a single gene or by closely linked homologous genes that have been identified. This genetic basis distinguishes a system from looser groupings such as collections or series.

Why are ABO and Rh the most important blood group systems?

ABO antibodies occur naturally and can cause immediate, severe haemolysis if incompatible blood is given, while the Rh D antigen is highly immunogenic and a leading cause of alloimmunisation and haemolytic disease of the fetus and newborn. Both are therefore typed for every transfusion.