Duffy Antigen Receptor for Chemokine (DARC) Polymorphisms and Its Involvement in Acquisition of Inhibitory Anti-Duffy Binding Protein II (DBPII) Immunity

Flávia A Souza-Silva,Cristiana F A Brito,Bruno A M Sanchez,Luzia H Carvalho,Tais N Sousa,Letícia M Torres,Flora S Kano,Michaelis Loren Tang,Cor J F Fontes,John H Adams,Jessica R Santos-Alves,Paulo A Nogueira,Roberto S Rocha,Kevin Ka Tetteh

doi:10.1371/journal.pone.0093782

Abstract

The Plasmodium vivax Duffy binding protein (PvDBP) and its erythrocytic receptor, the Duffy antigen receptor for chemokines (DARC), are involved in the major P. vivax erythrocyte invasion pathway. An open cohort study to analyze DARC genotypes and their relationship to PvDBP immune responses was carried out in 620 volunteers in an agricultural settlement of the Brazilian Amazon. Three cross-sectional surveys were conducted at 6-month intervals, comprising 395, 410, and 407 subjects, respectively. The incidence rates of P. vivax infection was 2.32 malaria episodes per 100 person-months under survey (95% confidence interval [CI] of 1.92-2.80/100 person-month) and, of P. falciparum, 0.04 per 100 person-months (95% CI of 0.007–0.14/100 person-month). The distribution of DARC genotypes was consistent with the heterogeneous ethnic origins of the Amazon population, with a predominance of non-silent DARC alleles: FY*A > FY*B. The 12-month follow-up study demonstrated no association between DARC genotypes and total IgG antibodies as measured by ELISA targeting PvDBP (region II, DBPII or regions II–IV, DBPII-IV). The naturally acquired DBPII specific binding inhibitory antibodies (BIAbs) tended to be more frequent in heterozygous individuals carrying a DARC-silent allele (FY*BES). These results provide evidence that DARC polymorphisms may influence the naturally acquired inhibitory anti-Duffy binding protein II immunity.

Highlights

Plasmodium vivax is the most widespread Plasmodium species and is a potential cause of morbidity and mortality among the 2.48 billion people living at risk of infection [1]
At the time of first blood collection, 19 (3%) subjects had positive bloodsmears, with 17 (90%) of these infections caused by P. vivax
Since Duffy antigen receptor for chemokines (DARC) polymorphisms are suspected to affect the ability of Plasmodium vivax Duffy binding protein (PvDBP) antibodies to block parasite invasion [36], we carried-out the first follow-up population-based study of the relationship between DARC polymorphisms and DBP antibodies

Summary

Introduction

Plasmodium vivax is the most widespread Plasmodium species and is a potential cause of morbidity and mortality among the 2.48 billion people living at risk of infection [1]. Plasmodium vivax infects human erythrocytes (RBCs) through a pathway that requires interaction between an apical parasite protein, the Duffy binding protein (PvDBP), and its receptor on reticulocytes, the Duffy antigen receptor for chemokines (DARC) [4,5,6]. The goal in developing PvDBP as a vaccine against blood stages of P. vivax is to elicit an antibody response that inhibits parasite adhesion to DARC-positive human reticulocytes, and thereby prevents merozoite invasion. The importance of the interaction between PvDBP (region II, DBPII) and DARC to P. vivax infection has stimulated a significant number of studies of PvDBP antibody responses. Available data demonstrate that naturally occurring antibodies to PvDBP are prevalent in individuals living in P. vivax endemic areas [7,8,9], and these antibodies can block the DBPII/ DARC interaction [10,11,12]. Anti-PvDBP immune responses have been well characterized, little is known about the association between this immune response and DARC host genotype [14,15]

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Results

Conclusion