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

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.

Plasmodium simium, a Plasmodium vivax-Related Malaria Parasite: Genetic Variability of Duffy Binding Protein II and the Duffy Antigen/Receptor for Chemokines

“…The P . simium erythrocyte invasion pathway was not the focus of the current work, but the availability of transfected COS cells expressing PvDBPII [ 48 ] offered an opportunity to gain insight into the biology of invasion. The in vitro experiments demonstrated that A .…”

The Presence, Persistence and Functional Properties of Plasmodium vivax Duffy Binding Protein II Antibodies Are Influenced by HLA Class II Allelic Variants

“…The study population was quite stable. Most residents were native to the Amazon region, and their average age of 28 years roughly corresponded to the time of malaria exposure in the Amazon area [7]. In the study area, migration rates were relatively low, as only 28 (8%) of 336 individuals moved out of the village during the follow-up period.…”

“…The study site and malaria transmission patterns have been described in detail elsewhere [7]. Although P .…”

“…The available data demonstrate that naturally occurring antibodies to DBP are prevalent amongst individuals living in P . vivax endemic areas, and that these antibodies can inhibit the DBPII-DARC interaction [7, 9–12]. Even though DBPII-specific binding inhibitory antibodies (DBPII BIAbs) seem to confer a degree of protection against blood stage infection [11], the majority of people naturally exposed to P .…”

“…On the host side, recent evidence suggests that host genetic polymorphisms might also affect humoral immunity against DBP [15, 16], with DARC polymorphisms thought to affect the ability of DBP antibodies to block parasite invasion [16]. In a previous study, we demonstrated that the naturally acquired BIAbs response tended to be more frequent in heterozygous individuals carrying a DARC-silent allele ( FY*B ES ), which suggested that gene-dosage effect occurred [7]. In this context, we were interested in determining if DBPII non-responsiveness could be associated with variation in the major histocompatibility complex.…”