Antibody responses to Plasmodium falciparum: evolution according to the severity of a prior clinical episode and association with subsequent reinfection.

Abstract

Abstract. We measured sporozoite-and total parasite antigen-specific IgG and IgM antibodies before and after treatment in matched groups of Gabonese children who presented with either mild or severe Plasmodium falciparum malaria. We investigated the influence of various parameters on these antibody responses, including clinical presentation, age, and post-treatment reinfection profiles. IgG but not IgM responses were strongly influenced by both clinical and parasitological status. IgG responses to the repeat region of the circumsporozoite protein, which were low at admission, particularly so in those with severe anemia, increased after treatment but showed no association with either age or reinfection profiles. Total parasite antigen-specific IgG responses were strongly influenced by parasitological status, and also differed significantly when segregated according to clinical status at admission, age, and reinfection histories. Most notably, anti-parasite IgG responses measured when children were parasite-free were higher and a good indicator of recent reinfections in those who presented with mild rather than with severe malaria. The profile of responses in the latter group suggests some immune system dysfunction, which may reflect the induction of tolerance to parasite antigens.

Immunoglobulin G Isotype Responses to Erythrocyte Surface-Expressed Variant Antigens of Plasmodium falciparum Predict Protection from Malaria in African Children

“…Self-evidently, in the study described here the children who presented with severe malaria lacked effective immune responses capable of suppressing the growth of the parasites responsible for their condition. Despite the relatively greater susceptibility to malaria and the relatively poorer persistence of parasite antigen-specific antibodies within this particular group (19,(23)(24)(25), the findings we present here nevertheless suggest that an ability to produce larger amounts of anti-VSA antibodies with specificity for determinants expressed by heterologous parasite isolates is associated with a benefit to some of these children in the form of a degree of protection from malaria.…”

Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children.

“…These profiles are in accordance with our own observations, in the same cohort of children, showing that antibody hyporesponsiveness to a crude preparation of asexual stage antigens of P. falciparum is a feature of those who presented with severe malaria. 46 Individuals with persistently low heterologous anti-VSA IgG responses have been reported by others, although a specific association with the severity of clinical outcome has not been identified and their frequency at the population level is not known. 5,31 Heterologous anti-VSA IgG responses in those with severe malaria also may have a significantly shorter half-life than the equivalent responses in children with mild malaria if, for example, they are dominated by short-lived IgG3 responses.…”

FatalPlasmodium falciparumMalaria Causes Specific Patterns of Splenic Architectural Disorganization

“…Humoral immune responses play an important part in the development of clinical immunity to malaria (7,24). Although exposure may lead to the accumulation of a repertoire of antibodies to variant and conserved parasite antigens, these responses are often short lived and depend on the presence of parasites, suggesting that there are inadequate memory B-cell responses or T-cell help (8,10,17,30). Our observations of the depletion of B cells from the marginal zone and the lack of germinal center formation indicate that B-cell maturation and migration are perturbed in malaria, and the causes of this are unclear.…”