Present Status of the Duffy Blood Group System: Articles Reviewed

Abstract

The Duffy blood group has five antigenic specificities, Fy^a, Fy^b, Fy3, Fy4, and Fy5, that are part of, or related to, the system. The first four antigens are under the genetic control of a locus near the centromere of chromosome 1. Fy5 antigen is absent on red cells that lack both Fy^a and Fy^b, and it is also absent from cells that have the Rh_null phenotype. This suggests that Fy5 may require contributions by Duffy and Rhesus gene products for its synthesis or proper orientation on the cell membrane.

The great majority of Caucasians have an Fy^a or Fy^b gene (or both) inherited by strict Mendelian principles. No evidence has been found to suggest that independently segregating modifying genes affect the expression of Duffy. The frequency of different Duffy genes varies greatly in different sections of the world population. Aborigines of Australia and New Guinea have a high frequency of Fy^a, Fy^b is the most common gene in European Caucasians, and Negroes have a high frequency of an allele named Fy. Until recently, Fy was thought to represent an amorph, but the antibody named anti-Fy4 now seems to define an antigenic product. The exact genetic interrelationship of the different Duffy types is not yet clear, but it is possible that Fy^a and Fy^b are alleles and that Fy³ and Fy⁴ also have an allelic relationship at a Duffy sublocus.

Anti-Fy^a is most common of the Duffy antibodies and occurs most frequently in the serum of Caucasian patients who have been immunized by blood transfusion. The Fy^a antigen appears to be about 40 times less immunogenic than K of the Kell system. Fy^b is considerably less immunogenic than Fy^a, and about 1 serum with anti-Fy^b specificity is found for every 20 that are anti-Fy^a. Only a few examples of anti-Fy3, anti-Fy4, and anti-Fy5 have been found.

Incompatibility involving anti-Fy^a may cause severe reactions to blood transfusion. The Duffy antigens, with possible exception of Fy3, appear to be strongly active on fetal red cells, and on rare occasions anti-Fy^a may be responsible for hemolytic disease in the newborn. Anti-Fy^b does not appear to have as great a capability of producing severe in vivo hemolysis as does anti-Fy^a.

The Fy^a and Fy^b antigens of red cells are inactivated by various proteolytic enzymes, but they are not inactivated by neuraminidase. Sialic acid does not appear to be an essential component of the antigenic determinant. The Fy3, Fy4, and Fy5 antigens are not inactivated if red cells are treated with proteolytic enzymes. Duffy antigens appear to be thermolabile proteins and are not present in a soluble form in body secretions or in plasma. Phylogenetic studies in primates indicate that Fy^a may be a mutant found in man, but Fy^b is present in other primate species. Fy³ appears to be the oldest gene is evolutionary terms.