title: Southeast Asian ovalocytosis is associated with increased expression of Duffy antigen receptor for chemokines (DARC).
abstract: The Duffy antigen receptor for chemokines (DARC or Fy glycoprotein) carries antigens that are important in blood transfusion and is the main receptor used by Plasmodium vivax to invade reticulocytes. Southeast Asian ovalocytosis (SAO) results from an alteration in RBC membrane protein band 3 and is thought to mitigate susceptibility to falciparum malaria. Expression of some RBC antigens is suppressed by SAO, and we hypothesized that SAO may also reduce Fy expression, potentiallyleading to reduced susceptibility to vivax malaria. Blood samples were collected from individuals living in the Madang Province of Papua New Guinea. Samples were assayed using a flow cytometry assay for expression of Fy on the surface of RBC and reticulocytes by measuring the attachment of a phycoerythrin-labeled Fy6 antibody. Reticulocytes were detected using thiazole orange. The presence of the SAO mutation was confirmed by PCR. There was a small (approximately 10%) but statistically significant (p=0.049, Mann-Whitney U test) increase in Fy expression on SAO RBC compared with RBC from individuals without this polymorphism: mean Fy expression (mean fluorescence intensity [MFI]) was 10.12 +/- 1.22 for SAO heterozygotes versus an MFI of 8.95 +/- 1.1 for individuals without SAO. For reticulocytes the MFI values were 27.61 +/- 19.12 for SAO heterozygotes and 16.47 +/- 3.81 for controls. SAO is associated with increased and not decreased Fy6 expression so that susceptibility to P. vivax infection is unlikely to be affected.
authors.affiliation: Department of Infectious Diseases, Monash Medical Centre and Monash University, Clayton, Victoria, Australia.
authors.forename: I J
authors.initials: IJ
authors.lastname: Woolley
authors.forename: P
authors.initials: P
authors.lastname: Hutchinson
authors.forename: J C
authors.initials: JC
authors.lastname: Reeder
authors.forename: J W
authors.initials: JW
authors.lastname: Kazura
authors.forename: A
authors.initials: A
authors.lastname: Cortés
mesh_terms: D000293:Adolescent; D000328:Adult; D001210:Asia, Southeastern; D004198:Disease Susceptibility; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D016780:Malaria, Vivax / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000502:physiology*; D010966:Plasmodium vivax / Q000502:physiology*; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012156:Reticulocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface