Chagas' disease and Duffy antigen/receptor for chemokine (DARC): a mini-review

Abstract

Duffy gene (FY) codifies the transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system which were designated receptors for chemokines and denominated DARC (Duffy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing inflammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an inflammatory disease, in which infiltrated inflammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profile of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this inflammatory disease.Key words: DARC antigen, Duffy blood-group system, Chagas' disease, Chagas' cardiomyopathy. Review ARticle INTRODUCTIONThe Duffy gene (FY) codifies the moderately immunogenic transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa (1). This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system, which are codified by FYA and FYB alleles of the FY gene playing a codominant role. The FYA and FYB alleles differ due to substitution of the base G by another A in the 125 nucleotide, which develops a common polymorphism in the Caucasian population. This single nucleotide polymorphism (SNP) results in the substitution of amino acid glycine by asparagine in position 42 (2).Although this polymorphism originates distinct glycoproteins called Fya and Fyb antigens, both have moderate immunogenicity.They can be identified with the use of antiFya and anti-Fyb anti-sera, allowing the characterization of four erythrocyte phenotypes: Fy(a+b-), Fy(a-b+), Fy(a+b+) and Fy(a-b-) (3, 4). Negative phenotype Duffy [Fy(a-b-)] is the result of a variant FYB allele (FYB-33), which presents a single point mutation where there is a T to C substitution in nucleotide -33 (-33T>C), also known as the GATA-BOX, located in the promoter region of the FY gene (5, 6).The differential distribution of DARC antigenic determinant between ethnic groups is a characteristic of this histo-blood system. As an example, FYA is prevalent in European, Chinese, Japanese, and Malaysian populations, but rarely in African population. And on the other hand, in Caucasians, FYB is widely found compared to Asian and African populations (7, 8 (25)(26)(27)(28). Genetic mechanisms for the Duffy-negative phenotype in erythrocytes have preserved its expression in the endothelium determining an important role in inflammation physiopathology (16, 19).Antigens...

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

“…Chemokines are cytokines formed by small proteins involved in the recruitment of leukocytes to inflammation sites. [ 9 – 12 ]. They act via specific receptors belonging to the superfamily of G protein-coupled receptors with seven transmembrane domains.…”