title: HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites.
abstract: BACKGROUND
  Primigravid (PG) women are at risk for pregnancy-associated malaria (PAM). Multigravid (MG) women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM) expressed by chondroitin sulfate A (CSA)-adhering parasitized erythrocytes (PEs). We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response.
  
  
  RESULTS
  We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001). This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR) 18-195] versus 251 [IQR 93-397], p = 0.006) and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001) and IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001) than their HIV-negative MG counterparts.
  
  
  CONCLUSIONS
  Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Keen
authors.forename: Lena
authors.initials: L
authors.lastname: Serghides
authors.forename: Kodjo
authors.initials: K
authors.lastname: Ayi
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.forename: John
authors.initials: J
authors.lastname: Ayisi
authors.forename: Anne
authors.initials: A
authors.lastname: van Eijk
authors.forename: Richard
authors.initials: R
authors.lastname: Steketee
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D009115:Muridae; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D010920:Placenta / Q000276:immunology / Q000469:parasitology / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000469:parasitology / Q000821:virology; D015597:Pregnancy Complications, Parasitic / Q000276:immunology / Q000469:parasitology / Q000821:virology
chemical_list: D000954:Antigens, Surface; D007074:Immunoglobulin G; D009895:Opsonin Proteins