The role of naturally acquired cytophilic antibodies in protection from severe malaria: an epidemiological study on the Kenyan coast

Abstract

The prospect of developing a malaria vaccine is supported by the observation that children in endemic areas develop naturally acquired immunity to malarial disease. Naturally acquired immunity takes several years to develop and is characterised by a decrease in the frequency and severity of disease episodes. In recent years, there has been a growing interest in the different roles played by the four subclasses of IgG in the acquisition of naturally acquired immunity to malaria. A defence mechanism that involves the association of monocytes and antibodies has been proposed. IgG1 and IgG3 subclasses are thought to be particularly efficient at associating with monocytes and hav e been called "cytophilic antibodies". Conversely, non-cytophilic antibodies IgG2, and possibly IgG4 are proposed to be antagonistic to cyrtophilic antibody subclasses. This study tested the hypothesis that pre-existing cytophilic antibody subclasses to Plasmodium falciparum are protective against severe malaria in children living in a holoendemic area along the Kenyan coast. In May 1995, one month before the beginning of the malaria transmission season, blood samples were taken from 4817 children of ages between one and five years living in an area of seasonal malaria transmission in Kilifi district. Nineteen of these children who subsequently developed severe malaria during the following two malarial seasons were selected for the investigation (cases), and each was matched by age and home location to three children of those who remained healthy (controls). Enzyme linked immunosorbent assay (EL1SA) was used to measure IgG 1, IgG?, IgG3 and IgG4 antibodies in the pre-season serum samples to P. falciparunm schizonts and the levels in the cases and controls were compared. The levels of IgGl, IgG3 and IgG4 showed a positive association with protection against disease. In contrast, the levels of IgG? were negatively associated with protection. This supports the hypothesis that cytophilic antibodies are protective against malaria. The fact that IgG4, a non-cytophilic antibody correlated with protection was unexpected. However, this observation fits well with the affinity of the FcyR l and FcR sub-class Ilb receptors' specificity for human IgG subclass antibodies which decreases in the order; IgG3>IgG1>IgG4>>>IgG2and IgG3>IgG1>IgG4>>IgG2 respectively.