Effects of Pregnancy and Intensity of Plasmodium falciparum Transmission on Immunoglobulin G Subclass Responses to Variant Surface Antigens

Abstract

Placenta-sequestering Plasmodium falciparum involved in the pathogenesis of pregnancy-associated malaria (PAM) in otherwise clinically immune women expresses particular variant surface antigens (VSA _PAM ) on the surface of infected erythrocytes that differ from VSA found in parasitized nonpregnant individuals (non-PAM type VSA). We studied levels of immunoglobulin G (IgG) and IgG subclasses with specificity for VSA _PAM and for non-PAM type VSA in pregnant and nonpregnant women from two sites with different endemicities in Cameroon. We found that VSA _PAM -specific responses depended on the pregnancy status, parity, gestational age, and parasite transmission intensity, whereas only the parasite transmission intensity influenced the levels of IgG specific for non-PAM type VSA. For both types of VSA, the responses were dominated by the cytophilic subclass IgG1, followed by IgG3. In pregnant women, the levels of VSA _PAM -specific antibodies either were very low or negative or were very high, whereas the levels of the antibodies specific for non-PAM type VSA were uniformly high. Interestingly, the levels of VSA _PAM -specific IgG1 increased with increasing gestational age, while the levels of the corresponding IgG3 tended to decrease with increasing gestational age. The IgG subclass responses with specificity for non-PAM type VSA did not vary significantly with gestational age. Taken together, our data indicate that IgG1 and to a lesser extent IgG3 are the main subclasses involved in acquired VSA _PAM -specific immunity to pregnancy-associated malaria.