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Dean L. Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2005.

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Blood Groups and Red Cell Antigens [Internet].

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Chapter 9The Duffy blood group

The Duffy glycoprotein is a receptor for chemicals that are secreted by blood cells during inflammation. It also happens to be a receptor for Plasmodium vivax, a parasite that invades red blood cells (RBCs) and causes malaria. RBCs that lack the Duffy antigens are relatively resistant to invasion by P. vivax. This has influenced the variation in Duffy blood types seen in populations where malaria is common.

Antibodies formed against the Duffy antigens are a cause of both transfusion reactions and hemolytic disease of the newborn.

At a glance

Antigens of the Duffy blood group

Number of antigens 6: Fya, Fyb, Fy3, Fy4, Fy5, Fy6
Antigen specificity Protein
Amino acid sequence determines the specificity of Duffy antigens.
Antigen-carrying molecules Glycoprotein that is a red cell receptor
The Duffy glycoprotein is a receptor that binds cytokines released during inflammation. It also binds the malaria parasite Plasmodium vivax, and RBCs that lack the Duffy Fya and Fyb antigens are resistant to invasion. Structurally, the Duffy protein is similar to the family of G-protein coupled receptors, having 7 transmembrane domains.
Molecular basis The FY gene encodes the Duffy antigens.
FY has two major codominant alleles, FYA and FYB, which result from a SNP (125G→A), and the corresponding Fya and Fyb antigens differ by a single amino acid (G42D). Individuals who are homozygous for a -33T→C SNP in the erythroid promoter region of the FYB allele have the phenotype Fy(a-b-) and do not express Duffy antigens on their RBCs.
Frequency of Duffy antigens Fya: 66% Caucasians, 10% Blacks, 99% Asians
Fyb: 83% Caucasians, 23% Blacks, 18.5% Asians
Fy3: 100% Caucasians, 32% Blacks, 99.9% Asians (1).
Frequency of Duffy phenotypes The Duffy null phenotype, Fy(a-b-), is very rare in Caucasians but is found in 68% of Blacks (1).
Fy(a+b+): 49% Caucasians, 1% Blacks, 9% Chinese
Fy(a-b+): 34% Caucasians, 22% Blacks, <1% Chinese
Fy(a+b-): 17% Caucasians, 9% Blacks, 91% Chinese

Antibodies produced against Duffy antigens

Antibody type IgG
Mainly IgG, IgM is rare
Antibody reactivity Does not bind complement
Transfusion reaction Typically a moderate, delayed transfusion reaction
Anti-Fya and anti-Fyb can cause transfusion reactions that range from mild to severe in nature and may occur immediately after the transfusion (rarely) or more commonly, after a delay. Anti-Fy3 is a cause of mild to moderate, delayed transfusion reactions.
Hemolytic disease of the newborn Typically mild disease
Anti-Fya causes mild HDN (rarely, severe HDN can occur). Anti-Fyb and anti-Fy3 are uncommon causes of mild HDN.

Background information


The Duffy blood group was discovered in 1950. It was named for a patient with hemophilia who had received multiple blood transfusions and was the first known producer of anti-Fya. A year later, anti-Fyb was discovered in a woman who had had several children. The remaining Duffy antigens (FY3, FY4, FY5, and FY6) were discovered 20 years later, but from these, only FY3 appears to be clinically significant.

The frequency of the Duffy phenotypes varies in different populations. The Duffy null phenotype, Fy(a-b-), is rare among Caucasian and Asian populations, whereas it is the most common phenotype in Blacks, occurring in over two-thirds of the Black population. The racial variation in the distribution of Duffy antigens is a result of a positive selection pressure—the absence of Duffy antigens on RBCs makes the RBCs more resistant to invasion by a malarial parasite.

Worldwide, of the four Plasmodium species that routinely cause malaria in humans, P. falciparum is responsible for the majority of fatal cases (2). But in Asia and the Americas, P. vivax is a more common cause of malaria. To cause disease, P. vivax must first enter the human RBC, which it does by binding to the N-terminal extracellular domain of the Duffy glycoprotein through the cysteine-rich region of the Duffy binding protein (DBP) (3). Individuals with the Duffy null phenotype do not express the Duffy protein on their RBCs and therefore are immune to P. vivax infection.

Interestingly, the Fy(a-b-) phenotype is most common in areas where there is little P. vivax malaria (4). In areas of West Africa, there is a high frequency of the Fy (a-b-) phenotype and a low incidence of P. vivax malaria. This may be because the pre-existence of a high frequency of the Fy(a-b-) phenotype prevented P. vivax malaria from becoming endemic in West Africa (4, 5).


  • Number of Duffy antigens: 6
  • ISBT symbol: FY
  • ISBT number: 008
  • Gene symbol: FY
  • Gene name: Duffy blood group

Basic biochemistry

The Duffy glycoprotein is encoded by the FY gene, of which there are two main alleles, FYA and FYB. They are codominant, meaning that is the FYA is inherited from one parent and the FYB allele if inherited from the other, both gene products, Duffy Fya and Fyb antigens, will be expressed on the RBCs.


There are four main Duffy phenotypes:

  • Fy(a+b-)
  • Fy(a+b+)
  • Fy(a-b+)
  • Fy(a-b-)

The Fya and Fyb antigens are found relatively frequently in Caucasians (Fya 66% and Fyb 83%) and Asians (Fya 99% and Fyb 18.5%) but are far less common in Blacks (Fya 10% and Fyb 23%). In fact, the Fy(a- b-) phenotype is present in two-thirds of African-American Blacks but is very rare in Caucasians (1).

An important minor Duffy phenotype is the Fyx [Fy(b+x)]. The FYX allele encodes the Fyb antigen, but it is only weakly expressed because a reduced amount of Duffy protein, and it is not always detected by anti-Fyb.

Expression of Duffy antigens

Duffy antigens are expressed on many different types of cells. Even Fy(a-b-) individuals who do not produce Duffy antigens on their RBCs do express Duffy antigens elsewhere, including endothelial cells that line blood vessels, epithelial cells of kidney collecting ducts, lung alveoli, and Purkinje cells of the cerebellum. Duffy antigens are also expressed in the thyroid gland, the colon, and the spleen.

Function of Duffy glycoprotein

The Duffy glycoprotein is also called the Duffy-Antigen Chemokine Receptor (DARC). As a chemokine receptor, it binds to the chemicals that are secreted by cells during inflammation and recruits other blood cells to the area of damage. These chemokines include C-X-R (acute inflammation chemokine) and C-C (chronic inflammation chemokine), IL-8 (interleukin 8), and RANTES (regulated on activation, normal T-expressed and secreted) (6).

Animal studies suggest that the function of Duffy as a chemokine receptor is not physiologically important because mice that lacked the mouse homolog of the Duffy gene (Dfy) were not more susceptible to infection than mice that expressed Dfy (7). Indeed, individuals with the null Duffy phenotype appear to have normal RBCs and a normal immune system.

Clinical significance of Duffy antibodies

Transfusion reactions

Antibodies against the Duffy antigens Fya (8), Fyb (9, 10), Fy3 (1), and Fy5 (11,12) have all been implicated as the cause of a transfusion reaction. Anti-Fya is more commonly found in patients who are of African descent (in whom the Duffy null phenotype is more common) and have sickle cell anemia (and therefore may require multiple blood transfusions).

Hemolytic disease of the newborn

Maternal-fetal incompatibilities within the Duffy blood group system is an uncommon cause of HDN. The disease tends to be mild in nature. The Duffy antigens known to have caused maternal immunization and subsequent hemolytic disease are Fya (13-16), Fyb (17), and Fy3 (1).

Molecular information


The Duffy locus, FY, is located on chromosome 1 at position q22-q23. It consists of two exons that span over 1,500 bp of genomic DNA. The two main alleles, FYA and FYB, differ by a single nucleotide at position 125 (G and A, respectively) and they likewise encode Fya and Fyb antigens that differ by a single amino acid at residue 42 (glycine and aspartic acid, respectively).

View the sequences of FY alleles at the
dbRBC Sequence Alignment Viewer

There are two genetic backgrounds that give rise to the Duffy negative phenotype Fy(a-b-) (18). Most commonly, a mutation in the promoter region of the FYB allele abolishes the expression of the Duffy glycoprotein in RBCs, but the protein is still produced in other types of cells. This erythroid-specific mutation is found in African Americans (70%) and West Africans (approaching 100%) (19). Perhaps because the Duffy antigens are expressed in other tissues, these patients do not generally make anti-Fyb or anti-Fy3 (20).

Less commonly, the Fy(a-b-) phenotype is a result of point mutation that introduces a premature stop codon into the coding sequence. It is unlikely that the truncated Duffy protein is transported to the cell surface, and it is likely that the Duffy protein would be absent from all tissues in individuals who carry this type of mutation. There may be strong anti-Fy3 in these patients (20).

The molecular basis of the Fx [Fy(b+x)] phenotype is a mutation in the coding sequence 265C→T (Arg897Cys), which always occurs with another mutation, 298G→A (Ala100Thr) (18).


The Duffy glycoprotein is a transmembrane protein that spans the RBC membrane seven times and has an extracellular N-terminal domain and a cytoplasmic C-terminal domain. It shares structural similarity with G-protein coupled receptors but so far, it has not been shown to be a member of this family.

The binding site for chemokines, the binding site for P. vivax, and the major antigenic domains are all located in overlapping regions in the extracellular N-terminal domain.


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