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.

IgG isotypic antibodies to crude <i>Plasmodium falciparum</i> blood-stage antigen associated with placental malaria infection in parturient Cameroonian women

“…Antibody responses to a crude P. falciparum blood stage extract in parturient women were predominantly cytophilic given the higher levels and prevalence rates of IgG1 and IgG3 subclasses seen relative to IgG2 and IgG4. These findings are in accordance with reports from previous studies 13,15,20 . Similarly, VSAPAM -specific IgG subclass responses in pregnancy are dominated by IgG1 and IgG3 antibodies as reported by Megnekou et al 13 and Eliott et al 15 .…”

“…These findings are in accordance with reports from previous studies 13,15,20 . Similarly, VSAPAM -specific IgG subclass responses in pregnancy are dominated by IgG1 and IgG3 antibodies as reported by Megnekou et al 13 and Eliott et al 15 . Cytophilic antibodies are usually produced together 15 .…”

“…Studies have shown that the responses for both non-VSA-PAM 13,14 and VSAPAM [10][11][12][13][14][15] are dominated by the cytophilic subclass IgG1, followed by IgG3 consistent with data obtained from non-pregnant adults and children 14,16,17 . The predominance of IgG1 and IgG3 cytophilic antibody in endemic areas has been associated with either lower parasitaemia 18 or a lower risk of malaria attack 19 .…”

Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway

“…However, as cytophilic antibodies have been collected from infected pregnant women (39), it should be borne in mind that other antibodydependent mechanisms, such as phagocytosis and complement activation, may also help to protect against PAM, in addition to blocking adhesion. Consistent with the existence of additional antibody mechanisms, Megnekou et al (40) showed that IgG1 and IgG3 were the most prevalent subclasses of PAM antibodies in Cameroonian women, and that larger amounts of these antibodies were found in pregnant multiparous women.…”

Changing Trends inP. falciparumBurden, Immunity, and Disease in Pregnancy

“…Moreover, levels of IgG antibodies against CS2 were increased in women with qPCR-positive P. falciparum infection at delivery. 16,17 These results indicate a close relationship between antibody levels and the intensity of malaria transmission [16][17][18][34][35][36] and suggest that antibodies against VAR2CSA may be a marker for cumulative exposure to the parasite during pregnancy. 19 More important, this study shows that 5 years of a marked decline in the prevalence of malaria was accompanied by reductions in levels of IgG antibodies against CS2 parasites by a factor of 2.8 and by reductions in IgG antibodies against antigens that are not specific to pregnancy, as well as by an increase in the geometric mean of parasite densities and a larger adverse effect of these infections on maternal hemoglobin levels and the weight of newborns.…”