Duffy blood group system, classification of human blood based on the presence of glycoproteins known as Fy antigens on the surface of red blood cells, endothelial cells (cells lining the inner surface of blood vessels), and epithelial cells in the alveoli of the lungs and in the collecting tubules of the kidneys. The Duffy antigens Fya (Fy1) and Fyb (Fy2) were discovered in 1950 and 1951, respectively. The antigens are named after the patient in whom Fya antibodies were first detected.
The Duffy antigens act as receptors for substances called chemokines, which are hormonelike molecules that attract cells of the immune system to particular sites in the body. The Duffy antigens also serve as receptors for the malarial parasites Plasmodium knowlesi and P. vivax. There are four possible Fy phenotypes: Fya+b+, Fya+b−, Fya−b+, and Fya−b−. The Fya+b+ phenotype is the most common in Caucasians, occurring in nearly 50 percent of the population; phenotype Fya+b− occurs in some 90 percent of individuals of Chinese descent and in less than 20 percent of Caucasians; phenotype Fya−b+ occurs in about 34 percent of Caucasians and 22 percent of African Americans; and phenotype Fya−b− occurs in nearly 70 percent of individuals of African descent and is very rare in Caucasians. Because the Duffy antigens are not expressed in the Fya−b− phenotype—and hence there are no receptors to which malarial parasites can bind—the null condition is associated with some degree of protection against malaria. Research has indicated that the increased frequency of the Fya−b− phenotype in West Africans and African Americans is the result of natural selection for disease resistance.
The Duffy antigens arise from variations in a gene known as DARC, which encodes the chemokine receptor protein found on the surfaces of Duffy-expressing cells. Antibodies to Duffy antigens designated Fy3 through Fy5 were discovered in the early 1970s, and in the following decade antibodies to another antigen, Fy6, were discovered. The Fy3 through Fy6 antigens represent variations in the Fya and Fyb epitopes, which are the portions of antigens that are capable of stimulating immune responses.
Duffy antigens also have been found on the surfaces of Purkinje cells in the brain and on cells of the colon, spleen, and thyroid gland. Antibodies to the Duffy antigens have been associated with transfusion reactions and with erythroblastosis fetalis (hemolytic disease of the newborn).