Method for assessing the immunogenicity of blood group antigens and clinical significance of erythrocyte antibodies

The clinical significance of blood group antigens is determined by their ability to stimulate the formation of alloantibodies in response to red blood cell transfusions. The frequency of antibody detection in recipients exhibits country-specific characteristics and depends on the antigenic diversity of the population, the use of anti-Rh immunoglobulin, and the implementation of alloimmunization prevention strategies in transfusion therapy. The effects of antibodies in transfusions involving incompatible erythrocytes range widely—from mild symptomatic anemia to life-threatening complications.

The conducted analysis of large-scale immunohematological studies allowed for the classification of antigens into highly immunogenic—D, E, K (Kell); moderately immunogenic—C, c, Jk^a (Kidd), Fy^a (Duffy), M (MNS), Le^a (Lewis); and low-immunogenic—other erythrocyte antigens. Analysis of annual SHOT (Serious Hazards of Transfusion, UK) and FDA (Food and Drug Administration, USA) reports showed that monospecific antibodies to Jk^a, Jk^b, Fy^a, c, and E antigens account for the majority of delayed hemolytic reactions, whereas antibodies to K, Fy^a, c, Jk^a, and Jk^b antigens are responsible for most transfusion-related fatalities.

A review of studies on the immunological safety of erythrocyte transfusions led to the development of a method for quantitatively assessing the immunogenicity of antigens and the clinical significance of monospecific antibodies. Each erythrocyte antigen was assigned a numerical value expressed in arbitrary units. This antigen significance factor can be used in phenotypic donor matching—including via software—and in selecting erythrocytes with the lowest clinical risk of alloimmunization and transfusion complications in critical situations when blood components fully matched to the recipient’s phenotype are unavailable.