The duffy protein: A malarial and chemokine receptor

doi:10.1016/S0037-1963(00)90037-4

Seminars in Hematology

Volume 37, Issue 2, April 2000, Pages 122-129

https://doi.org/10.1016/S0037-1963(00)90037-4 Get rights and content

Abstract

A major advance towards understanding the Duffy blood group system has been achieved with the cloning of FY, a single-copy gene located in the 1q22→q23 region of chromosome 1. The product of FY is an acidic glycoprotein (gp-Fy), which spans the plasma membrane seven times and has an exocellular N-terminal domain and an endocellular C-terminal domain. The system consists of four alleles, five phenotypes, and five antigens. FYA, FYB, FYB^ES, and FYB^WK are the alleles; Fy(a + b −), Fy(a − b +), Fy(a + b +), Fy(a − b + ^wK), and Fy(a − b −), are the phenotypes, and Fy^a, Fy^b, Fy3, Fy5, and Fy6 are the antigens. Fy(a − b −), or Duffy-negative individuals, lack the Duffy protein on erythrocytes and are predominantly African and American blacks. They have the FYB^ES allele with a mutation in the promoter region, which abolishes the expression of the protein in erythrocytes only. In the few cases of non-black Fy(a − b −) individuals, a nonsense mutation prevents the synthesis of gp-Fy. In Fy(a − b + ^wK) erythrocytes, the Fy^b antigen is weakly expressed due to a reduced amount of the protein. The Fy5 antigen includes the Rh protein, and the Fy6 antigen is defined by a murine monoclonal antibody. Gp-Fy is produced in several cell types, including endothelial cells of capillary and postcapillary venules, epithelial cells of kidney collecting ducts, and lung alveoli, as well as Purkinje cells of the cerebellum. The Duffy protein plays a role in inflammation and in malaria infection. The protein is a member of the superfamily of chemokine receptors and is the receptor to which certain malarial parasites bind to invade red blood cells. The parasite-specific binding site, the binding site of chemokines, and the major antigenic domains are located in overlapping regions at the exocellular N terminus of the Duffy protein.

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Cited by (92)

Blood Group Serotyping and Genotyping
2022, Encyclopedia of Infection and Immunity
According to the International Society of Blood Transfusion (ISBT) database, the human genome harbors sequence variations producing 346 serologically distinct red blood cell (RBC) antigen phenotypes resided at 45 genomic loci. ABO group is determined by ABO gene which encodes for four antigens, A, B, AB, and O. Together with, Rh group is determined by two genes, namely RHD and RHCE, which produces more than 200 RHD and 80 RHCE alleles and 50 different antigens. Together with, there are several blood group systems such as MNS, Kell, Lutheran antigens, Kidd, and Duffy, etc., but not limited. This high number of phenotypic differences in RBC antigens generates varied protein epitopes which differ from person to person. Additionally, platelets express antigens such as ABO as well as RhD blood groups. After transfusion, the immune system either tolerates these variations or generates adverse immune reactions. Therefore, developing genotyping methods as well as the serological methods (phenotyping) is of great importance. This article summarizes the most recent studies on serological and genotypic methods to determine blood group.
Duffy blood group system and ocular toxoplasmosis
2020, Infection, Genetics and Evolution
Citation Excerpt :
However, our data do not support this proposition. The arguments of Chaves Jorge et al. (2003)(Chaves Jorge et al., 2003) are supported by the demonstrations that Duffy blood group antigens have important role in the invasion of human erythrocytes by Plasmodium vivax (Kaur et al., 2019; King et al., 2011; Pogo and Chaudhuri, 2000) and Babesia divergens (La Hoz and Morris, 2019; Nakamoto et al., 1998; Sevilla et al., 2018; Suarez et al., 2019). Further studies with large numbers of patients from different populations would be required to validate this association since the frequencies of the Duffy phenotypes vary considerably between the ethnicities.
Duffy blood group phenotypes [Fy(a + b-), Fy(a-b+), Fy(a + b+), Fy(a-b-)], characterized by the expression of Fy^a, and Fy^b antigens, are present in red blood cells. Therefore, we hypothesize that the non-hematopoietic expression of these antigens might influence cell invasion by T. gondii.
576 consecutive patients from both genders were enrolled. The presumed OT clinical diagnosis was performed. Duffy phenotyping was performed by hemagglutination in gel columns and for the correct molecular characterization Fy(a-b-) phenotype, using PCR-RFLP. Anti-T. gondii IgG antibodies were detected by ELISA. Chi-square, Fisher's exact tests were used to compare the proportions.
OT was present in 22.9% (n = 132) and absent in 77.1% (n = 444) of patients. The frequencies of anti-T. gondii IgG antibodies were higher in OT (127/132, 96.2%) than those without this disease (321/444, 72.3%) (p < .0001). None of the Duffy antigens or phenotypes were associated with T. gondii infection (χ2: 2.222, GL: 3, p = .5276) as well as the risk of OT (χ2: 0.771, GL: 3, p = .8566).
Duffy blood group system phenotypes and their antigens do not constitute risk factors for infection by T. gondii infection and the development of OT.
Alloimmunization in Pregnancy
2020, Immunologic Concepts in Transfusion Medicine
Maternal alloimmunization is the presence of non-AB antibodies in the-pregnant woman, in some cases putting her fetus at risk for hemolytic disease of the fetus and newborn. While Anti-D is the best known isoimmunization and the most likely to cause severe HDFN, many other blood groups have been implicated and should be of concern to clinicians and blood banks. Early detection, risk mitigation, preventative RhIG administration, treatment of maternal and fetal anemia, and conservative transfusion with consideration of antigen matching improves outcomes and limits the chances for additional alloimmunization. Several recent studies are beginning to elucidate the mechanisms behind isoimmunization.
Duffy blood group system – the frequency of Duffy antigen polymorphisms and novel mutations in the Polish population
2019, Transfusion and Apheresis Science
Citation Excerpt :
The Duffy-negative phenotype Fy(a−b−), frequent in Africans, but very rare in Caucasians, is defined by the homozygous state of FY*02N.01alleles, associated with a SNP c.-67T > C in the promoter region of the FY gene, which suppresses erythroid expression of this gene without affecting its expression in other tissues [1,2]. The GATA-1 mutation c.-67T > C has been previously reported as -33 and -46 [6–8]. The same mutation has been identified in the promoter region of FY*A allele but it is very rare [9,10].
Duffy blood group genes are highly polymorphic with the distribution of alleles varying between different populations and ethnic groups. The aim of this study was to genotype Duffy blood group antigens and to establish FY alleles frequency in the Polish population and screen for novel FY gene mutations. Duffy phenotype and genotype frequencies analysis was based on studies of 596 persons. All these subjects were genotyped by high-resolution melting (HRM) method. It was shown that phenotype Fy(a+b+), defined by genotypes FY*A/FY*B (33%), FY*A/FY*B298A (13%), and FY*A/FY*02W.01 (2.8%) was the most common in Polish population (˜49%), followed by Fy(a−b+), ˜29%, determined by genotypes arising from FY*B allele and all its variants. Fy(a+b−) phenotype occurred with a frequency of 21.3% and was defined by the following genotypes: FY*A/A (21%), and FY*A/02N.01 (0.3%). Among the Polish population the frequencies of FY*A, FY*B, and FY*B298A alleles were 45.7%, 36% and 15.5%, respectively. The alleles FY*B298A and FY*B combined together, represented higher frequency (51%) than FY*A. Alleles FY*02W.01 and FY*02N.01 had frequencies 2.51% and 0.25%, respectively. The distribution of Duffy genotypes in the Polish population was in accordance with Hardy-Weinberg equilibrium (p = 0.9682). Alleles in the genotypes are independent from each other (r = 0.0278, R² = 0.00077). New mutations identified in the promoter region (c.-79T > C) and the coding region of the FY gene (c.147C > A and c.175 G > A) did not affect the Duffy antigen expression on erythrocyte. Although FY alleles frequency is known in different populations, no data for Polish population is available.
Frequencies of Duffy blood group alleles in Northern Pakistani donors
2014, Transfusion and Apheresis Science
Find the allele frequencies of Duffy blood group antigens in donor population from northern Pakistan.
Cross sectional study.
Armed Forces Institute of Transfusion (AFIT), Rawalpindi in year 2012.
A total of 1000 healthy, adult blood donors were included in the study. Blood samples were collected in ethylenediamine tetra aceticacid (EDTA) tube and then tested with anti sera Fy^a and Fy^b by the tube method.
The allele frequencies of Duffy blood group antigens were calculated. The most common phenotype was Fy(a+b+) which was present in 552 (55.2%) donors followed by the Fy(a+b-) phenotype in 228 (22.8%) donors, while 178 (17.8%) were Fy(a-b+) and the least prevalent phenotype was Fy(a-b-) which was present in 42 (4.2%) of donors.
The majority of our population is heterozygous for Duffy antigens a and b.
Duffy blood group genotypes among malaria Plasmodium vivax patients of Baoulch population in southeastern Iran
2014, Asian Pacific Journal of Tropical Medicine
To determine the distribution of Duffy blood group genotypes in Balouch population as a major ethnic group that living in a sub-tropical area in south East of Iran.
In this study, the Duffy blood group FY phenotypes were determined using indirect anti-globulin technique and also genotype by PCR-RFLP in 160 vivax malaria patients and 160 control individuals.
The results showed that the most common Duffy genotype was FYA/FYB (46.6%) followed by FYA/FYA (15.3%), FYA/FYO (14.4%), FYB/FYO (11.9%), FYB/FYB (10%) and FYO/FYO (1.9%). In case individuals, frequency of FYA, FYB and FYO alleles were 0.471, 0.431 and 0.097, respectively compaired to 0.444, 0.353 and 0.203, respectively in control (non-infected) group.
This data provide evidence that individuals with the FYA/FYB genotype have higher susceptibility to malaria and there are significant associations between Duffy blood group variants and susceptibility or resistance to vivax malaria.

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^☆: Supported by Specialized Center of Research (SCOR) Grant No. 54453 to A.O.P.

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The duffy protein: A malarial and chemokine receptor☆

Abstract

Blood

Blood

J Biol Chem

J Biol Chem

TIBS

Genomics

Cell

Blood

Blood

Blood

TIBS

J Biol Chem

Blood

Cell

Mol Immunol

J Biol Chem

A new antibody, anti-Fy3, in the Duffy blood group system

Vox Sang

Structural design and molecular evolution of a cytokine receptor superfamily

The Duffy Blood Group System

A new anti-erythrocyte antibody in the Duffy system: Anti-Fy4

Vox Sang

Human monoclonal antibody against Rh(D) antigen: Partial characterization of the Rh(D) polypeptide from human erythrocytes

Blood

An Alberta Cree Indian with a rare Duffy antibody, anti-Fy 3

Vox Sang

Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite

The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasite to erythrocytes

J Exp Med

The Duffy blood group system in Caucasians: Evidence for a new allele

Am J Hum Genet

Anti-Fy5 an antibody disclosing a probable association between the Rhesus and Duffy blood group genes

Vox Sang