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Duffy phenotypes in Malaysian populations: correction of previous unusual findings

Lewis GE, Miller LH, Ibrahim L, Wong PW, McGinniss M, Ooi WL

Trans R Soc Trop Med Hyg, 1988;82(3):509-10.
PMID: 3068862

Duffy phenotypes were determined for 314 Malaysian Orang Asli. The most common gene, Fya, was present in 313; there were no Duffy negative individuals. A previous study found evidence of Plasmodium vivax infection in 5 of 7 Orang Asli reported to be of the Duffy negative genotype. In this study, 5 of the 7 previously tested Orang Asli were retested in triplicate, and each of the 5 was found to be Duffy positive, having the Fya gene and a phenotype of Fy (a + b-).

Matched MeSH terms: Duffy Blood-Group System*
Fulltext Genotyping of the Duffy blood group among Plasmodium knowlesi-infected patients in Malaysia

De Silva JR, Lau YL, Fong MY

PLoS One, 2014;9(9):e108951.
PMID: 25268233 DOI: 10.1371/journal.pone.0108951

The Duffy blood group is of major interest in clinical medicine as it plays an important role in Plasmodium knowlesi and Plasmodium vivax infection. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Peninsular Malaysia were determined. The blood group of 60 healthy blood donors and 51 P. knowlesi malaria patients were genotyped using allele specific polymerase chain reaction (ASP-PCR). The data was analyzed using Fisher's exact test in order to assess the significance of the variables. Our results show a high proportion of the FY*A/FY*A genotype (>85% for both groups) and a high frequency of the FY*A allele (>90% for both groups). The FY*A/FY*A genotype was the most predominant genotype in both infected and healthy blood samples. The genotype frequency did not differ significantly between the donor blood and the malaria patient groups. Also, there was no significant correlation between susceptibility to P. knowlesi infection with any Duffy blood genotype.

Matched MeSH terms: Duffy Blood-Group System/classification; Duffy Blood-Group System/genetics*
Fulltext Erythrocyte-binding assays reveal higher binding of Plasmodium knowlesi Duffy binding protein to human Fya+/b+ erythrocytes than to Fya+/b- erythrocytes

Fong MY, Cheong FW, Lau YL

Parasit Vectors, 2018 Sep 26;11(1):527.
PMID: 30257710 DOI: 10.1186/s13071-018-3118-8

BACKGROUND: The merozoite of the zoonotic Plasmodium knowlesi invades human erythrocytes via the binding of its Duffy binding protein (PkDBPαII) to the Duffy antigen on the eythrocytes. The Duffy antigen has two immunologically distinct forms, Fya and Fyb. In this study, the erythrocyte-binding assay was used to quantitatively determine and compare the binding level of PkDBPαII to Fya+/b+ and Fya+/b- human erythrocytes.
RESULTS: In the erythrocyte-binding assay, binding level was determined by scoring the number of rosettes that were formed by erythrocytes surrounding transfected mammalian COS-7 cells which expressed PkDBPαII. The assay result revealed a significant difference in the binding level. The number of rosettes scored for Fya+/b+ was 1.64-fold higher than that of Fya+/b- (155.50 ± 34.32 and 94.75 ± 23.16 rosettes, respectively; t(6) = -2.935, P = 0.026).
CONCLUSIONS: The erythrocyte-binding assay provided a simple approach to quantitatively determine the binding level of PkDBPαII to the erythrocyte Duffy antigen. Using this assay, PkDBPαII was found to display higher binding to Fya+/b+ erythrocytes than to Fya+/b- erythrocytes.

Matched MeSH terms: Duffy Blood-Group System/genetics*; Duffy Blood-Group System/metabolism*
Erythrocyte Binding Activity of PkDBPαII of Plasmodium knowlesi Isolated from High and Low Parasitemia Cases

Mohd Bukhari FD, Lau YL, Fong MY

Am J Trop Med Hyg, 2020 Dec 14.
PMID: 33319732 DOI: 10.4269/ajtmh.20-0797

Invasion of Plasmodium knowlesi merozoite into human erythrocytes involves molecular interaction between the parasite's Duffy binding protein (PkDBPαII) and the Duffy antigen receptor for chemokines on the erythrocytes. This study investigates the binding activity of human erythrocyte with PkDBPαII of P. knowlesi isolates from high and low parasitemic patients in an erythrocyte binding assay. The binding activity was determined by counting the number and measuring the size of rosettes formed in the assay. The protein PkDBPαII of P. knowlesi isolated from low parasitemia cases produced significantly higher number of rosettes with human erythrocytes than high parasitemia case isolates (65.5 ± 12.9 and 17.2 ± 5.5, respectively). Interestingly, PkDBPαII of isolates from high parasitemia cases formed significantly larger rosettes with human erythrocytes than PkDBPαII of isolates from low parasitemia cases (18,000 ± 13,000 µm2 and 1,315 ± 623 µm2, respectively).

Matched MeSH terms: Duffy Blood-Group System
Potential combinatorial effects of recombinant atypical chemokine receptors in breast cancer cell invasion: A research perspective

Chew AL, Tan WY, Khoo BY

Biomed Rep, 2013 Mar;1(2):185-192.
PMID: 24648916

Apart from their major function in the coordination of leukocyte recruitment, chemokines, in cooperation with their receptors, have been implicated in the progression of various diseases including different types of cancer, affecting survival, proliferation and metastasis. A complex network of chemokines and receptors exists in the tumor microenvironment and affects tumor development in various ways where chemokines activate typical signalling pathways by binding to the respective receptors. The identification and characterization of a group of atypical chemokine receptors [D6, Duffy antigen receptor for chemokines (DARC), ChemoCentryx chemokine receptor (CCX-CKR) and CXCR7] which appear to use unique biochemical properties to regulate the biological activities of these chemokines, is useful in the effort to therapeutically manipulate chemokines in a broad spectrum of diseases in which these chemokines play a critical role. The aim of this review was to investigate the combinatorial effect of two reported atypical chemokine receptors, D6 and DARC, on breast cancer cell invasion to understand their role and therapeutic potential in cancer treatment. In this regard, findings of the present review should be confirmed via the construction of recombinant D6 and DARC clones as well as the expression of the respective recombinant proteins using the Pichia pastoris (P. pastoris) expression system is to be performed in a future study in order to support findings of the current review.

Matched MeSH terms: Duffy Blood-Group System
Fulltext Distribution of the Duffy genotypes in Malaysian Borneo and its relation to Plasmodium knowlesi malaria susceptibility

de Silva JR, Amir A, Lau YL, Ooi CH, Fong MY

PLoS One, 2019;14(9):e0222681.
PMID: 31536563 DOI: 10.1371/journal.pone.0222681

The Duffy blood group plays a key role in Plasmodium knowlesi and Plasmodium vivax invasion into human erythrocytes. The geographical distribution of the Duffy alleles differs between regions with the FY*A allele having high frequencies in many Asian populations, the FY*B allele is found predominately in European populations and the FY*Bes allele found predominantly in African regions. A previous study in Peninsular Malaysia indicated high homogeneity of the dominant FY*A/FY*A genotype. However, the distribution of the Duffy genotypes in Malaysian Borneo is currently unknown. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Malaysian Borneo were determined. A total of 79 P. knowlesi patient blood samples and 76 healthy donor samples were genotyped using allele specific polymerase chain reaction (ASP-PCR). Subsequently a P. knowlesi invasion assay was carried out on FY*AB/ FY*A and FY*A/ FY*A Duffy genotype blood to investigate if either genotype conferred increased susceptibility to P. knowlesi invasion. Our results show almost equal distribution between the homozygous FY*A/FY*A and heterozygous FY*A/FY*B genotypes. This is in stark contrast to the Duffy distribution in Peninsular Malaysia and the surrounding Southeast Asian region which is dominantly FY*A/FY*A. The mean percent invasion of FY*A/FY*A and FY*A/FY*B blood was not significantly different indicating that neither blood group confers increased susceptibility to P. knowlesi invasion.

Matched MeSH terms: Duffy Blood-Group System/genetics*
Fulltext Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

Kosaisavee V, Suwanarusk R, Chua ACY, Kyle DE, Malleret B, Zhang R, et al.

Blood, 2017 09 14;130(11):1357-1363.
PMID: 28698207 DOI: 10.1182/blood-2017-02-764787

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi-infected human reticulocytes that are strikingly similar to those observed for P vivax These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.

Matched MeSH terms: Duffy Blood-Group System/metabolism*
Sequence diversity and positive selection at the Duffy-binding protein genes of Plasmodium knowlesi and P. cynomolgi: Analysis of the complete coding sequences of Thai isolates

Putaporntip C, Kuamsab N, Jongwutiwes S

Infect Genet Evol, 2016 Oct;44:367-375.
PMID: 27480919 DOI: 10.1016/j.meegid.2016.07.040

Plasmodium knowlesi and P. cynomolgi are simian malaria parasites capable of causing symptomatic human infections. The interaction between the Duffy binding protein alpha on P. knowlesi merozoite and the Duffy-antigen receptor for chemokine (DARC) on human and macaque erythrocyte membrane is prerequisite for establishment of blood stage infection whereas DARC is not required for erythrocyte invasion by P. cynomolgi. To gain insights into the evolution of the PkDBP gene family comprising PkDBPα, PkDBPβ and PkDBPγ, and a member of the DBP gene family of P. cynomolgi (PcyDBP1), the complete coding sequences of these genes were analyzed from Thai field isolates and compared with the publicly available DBP sequences of P. vivax (PvDBP). The complete coding sequences of PkDBPα (n=11), PkDBPβ (n=11), PkDBPγ (n=10) and PcyDBP1 (n=11) were obtained from direct sequencing of the PCR products. Nucleotide diversity of DBP is highly variable across malaria species. PcyDBP1 displayed the greatest level of nucleotide diversity while all PkDBP gene members exhibited comparable levels of diversity. Positive selection occurred in domains I, II and IV of PvDBP and in domain V of PcyDBP1. Although deviation from neutrality was not detected in domain II of PkDBPα, a signature of positive selection was identified in the putative DARC binding site in this domain. The DBP gene families seem to have arisen following the model of concerted evolution because paralogs rather than orthologs are clustered in the phylogenetic tree. The presence of identical or closely related repeats exclusive for the PkDBP gene family suggests that duplication of gene members postdated their divergence from the ancestral PcyDBP and PvDBP lineages. Intragenic recombination was detected in all DBP genes of these malaria species. Despite the limited number of isolates, P. knowlesi from Thailand shared phylogenetically related domain II sequences of both PkDBPα and PkDBPγ with those from Peninsular Malaysia, consistent with their geographic proximity.

Matched MeSH terms: Duffy Blood-Group System