Duffy Antigen, malaria resistant

The Duffy antigen consists of a glycoprotein on the surface of erythrocytes that acts as a key mediator for the access of the Plasmodium vivax parasite to the interior of red blood cells during its life cycle. Thus, individuals who do not carry this antigen would be resistant to the forms of malaria caused by this species.

Malaria is an acute febrile illness caused by parasites of the Plasmodium genus, which are transmitted to humans through the bite of infected females of the Anopheles mosquito genus. The incidence has been established at around 60 cases per 1000 at-risk individuals annually, with a high mortality rate, especially among children, especially in resource-poor countries where the incidence is particularly high. There are five species of parasites that cause malaria in humans, of which the most dangerous are Plasmodium falciparum and vivax. Since the vector of transmission is a mosquito, it is usually restricted to tropical and subtropical areas where these insects thrive, however, while P falciparum is the most deadly malaria parasite and the most prevalent on the African continent.However, while P falciparum is the most deadly and most prevalent malaria parasite on the African continent, P vivax is the most widespread species outside Africa, accounting for 64% of cases in the Americas, more than 30% in Southeast Asia and 40% in the Eastern Mediterranean.

At a particular stage of the parasite's life cycle, the parasite must be able to gain access to the interior of erythrocytes. The Duffy antigen receptor for chemokines (DARC), also known as Duffy antigen, is a glycosylated erythrocyte cell surface protein that acts as a receptor for various chemokines (molecules responsible for chemically attracting various cell types). Its exact function is unknown, but it seems to be involved in the regulation of chemokine bioavailability and, consequently, the recruitment of leukocytes in different tissues. However, it has been reported that the Duffy antigen plays an important role in malaria transmission by acting as an erythroid receptor for P vivax. Thus, its absence (typical of African ancestry for which the most relevant parasite species is P falciparum), makes erythrocytes resistant to invasion by the P vivax species of the parasite. However, it is important to consider that there are other parasite species that can trigger malaria so that people who do not have the Duffy antigen can still be infected by these other forms of malaria. In addition, it has been suggested that DARC binding to platelet factor 4 (PF4) is essential for platelet-mediated clearance of P falciparum parasites, so in cases of infection by this other species, its absence may trigger a negative effect, however, these associations are still under investigation.

The presence or absence of the Duffy antigen in erythrocytes is highly heritable, although it is substantially more frequent in populations of African origin than in those of European origin. Through a study of 6000 individuals of African-American ancestry, a marker has been identified in the DARC or ACKR1 gene, responsible for the presence of this antigen in red blood cells or erythrocytes and resistance to malaria.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

1 variant

Bibliography

World Health Organizatio (WHO) Paludism. [May 2022]

Aldarweesh F. The Duffy Blood Group System. Human Blood Group Systems and Haemoglobinopathies. London: IntechOpen; 2019 [May 2022].

Kaur H et al. Duffy antigen receptor for chemokines (DARC) and susceptibility to Plasmodium vivax malaria. Parasitol Int. 2019 Aug;71:73-75.

Kano FS et al. Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Sci Rep. 2018 Sep 14;8(1):13851.

Reich D et al. Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene. PLoS Genet. 2009 Jan; 5(1): e1000360.

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