Duffy Blood Group System

Let's take a look at the Duffy blood group system. The presence of glycoproteins is called Fy antigens which are present 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 kidney collecting tubules are used to classify human blood in the Duffy blood group system. Duffy antigens Fya (Fy1) as well as Fyb (Fy2) were discovered in 1950 as well as 1951, respectively. The antigens are named after the first patient who developed Fya antibodies.

The Duffy antigens function as receptors for chemokines, which are hormone-like molecules that attract immune cells to specific sites in the body. The Duffy antigens are also receptors for the malaria parasites Plasmodium knowlesi and Plasmodium vivax.

There are four Fy phenotypes: Fya+b+, Fya+b−, Fya−b+, and Fya−b−. The Fya+b+ phenotype is the most common in Caucasians, accounting for nearly half of the population; phenotype Fya+b− occurs in approximately 90% of people of Chinese descent and less than 20% of Caucasians; phenotype Fya−b+ occurs in approximately 34% of Caucasians and 22% of African Americans, and phenotype occurs in Fya−b−. nearly 70% of people of African descent.

Because the Duffy antigens are not expressed in the Fya−b−  phenotype—and thus there are no receptors to which malarial parasites can bind—the null condition is known to be associated with some degree of malaria protection. According to research, the increased prevalence of the Fya−b−  phenotype in West Africans and African Americans is due to natural selection for disease resistance.

The Duffy antigens are the result of mutations in the DARC gene, which codes for the chemokine receptor protein found on the surfaces of Duffy-expressing cells. Antibodies to Duffy antigens Fy3 through Fy5 were basically discovered in the early 1970s, as well as the antibodies to another antigen, Fy6, were discovered the following decade. The Fy3–Fy6 antigens are variations on the Fya and Fyb epitopes, which are the parts of antigens capable of eliciting immune responses.

Duffy antigens have also been found on the surfaces of Purkinje cells in the brain as well as on cells of the colon, spleen, and thyroid gland in the human body. Antibodies to the Duffy antigens have been associated with transfusion reactions as well as with erythroblastosis fetalis (which is the hemolytic disease of the newborn).

Expression of Duffy Antigens

Duffy antigens are found on a wide range of cells. Even Fy(^a-b-) people who do not produce Duffy antigens on their RBCs (Red blood cells) express them elsewhere, including endothelial cells that line blood vessels, epithelial cells of the kidney collecting ducts, lung alveoli, as well as Purkinje cells in the cerebellum. Duffy antigens can also be found in the thyroid, colon, and spleen.

Function of Duffy Glycoprotein

Duffy glycoprotein is also referred to as the Duffy-Antigen Chemokine Receptor (DARC). It binds to chemicals secreted by cells during inflammation and recruits other blood cells to the site of damage as a chemokine receptor. C-X-R (acute inflammation chemokine) and C-C (chronic inflammation chemokine), IL-8 (interleukin 8), and RANTES are examples of these chemokines (regulated on activation, normal T-expressed and secreted).

Animal studies indicate that Duffy's function as a chemokine receptor is not physiologically important, as mice lacking the mouse homolog of the Duffy gene (Dfy) were not more susceptible to infection than mice expressing Dfy.

Indeed, individuals with the null Duffy phenotype appear to have normal RBCs as well as a normal immune system.

Duffy Antigen System

Six known antigens reside on a glycoprotein that acts as a chemokine receptor in the Duffy group system. Some malaria species use it as a receptor. The expression of Duffy antigens varies significantly across races. Approximately 68 percent of Blacks are deficient in both Fya and Fyb antigens. Individuals with this distinct phenotype are resistant to two types of malaria.

Antibodies that are generally formed against the Duffy antigens are of the IgG subclass as well as are clinically significant because they have been linked to acute and delayed hemolytic transfusion reactions, as well as foetal and newborn hemolytic disease. Patients who develop anti-Fya or anti-Fyb antibodies must be given antigen-negative blood units in the future.

Kell Duffy Kidd

The red blood cell (RBC) urea transporter is the Kidd (JK) glycoprotein. It is located in the membrane and rapidly transports urea into and out of RBCs while maintaining the osmotic stability and shape of the RBC. The Kidd glycoprotein is also expressed in the kidney, where it allows the kidney to accumulate a high concentration of urea required for the kidney to produce concentrated urine.

People who do not produce the Kidd glycoprotein are less able to concentrate urine, but they are healthy and their RBCs have a normal shape and lifespan.

Kidd antigen-specific antibodies are a major cause of delayed hemolytic transfusion reactions. Anti-Kidd antibodies are also known to be a cause of hemolytic disease of the newborn (HDN), the severity of which varies but is typically mild.