Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes.

Infection and Immunity
John P LusinguThor G Theander

Abstract

Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for ...Continue Reading

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Citations

Feb 12, 2008·The Journal of Infectious Diseases·Carlota DobañoJana S McBride
Jul 24, 2010·Malaria Journal·Bruno P MmbandoJohn P A Lusingu
Sep 24, 2010·PLoS Computational Biology·Thomas S RaskThomas Lavstsen
Jan 24, 2009·International Journal for Parasitology·Christian W WangThomas Lavstsen
Dec 19, 2007·PLoS Computational Biology·Jingchun ZhuDavid Haussler
Aug 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gerald K K ChamThor G Theander
Aug 16, 2017·BMC Infectious Diseases·Kevin CrokeBruno P Mmbando

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