Maternal transfer of immunoglobulin-g (igg) sub-types and its association to immunity against plasmodium falciparum infection among children in a Ugandan birth cohort (Busia-Eastern Uganda)

Abstract

Background: Children in malaria endemic area acquire maternal transferred immunity that is thought to be protective in their early months of life. Maternally transferred antibodies, mainly IgG play a critical role. IgG subclasses composition is important in malaria immunity but there is limited knowledge about their preferential transfer against a large panel of Pf antigens. This has been among very few if not first study in Uganda that looked at a large panel of 16 Plasmodium falciparum antigens across all four IgG subtypes with a large sample size intended to establish if maternal antibodies transferred to children born to mothers in malaria endemic area offers immune protection against Plasmodium falciparum infection in the first birth year. Aim of the Study: To assess maternal transfer of IgG subtypes and its association to development of immunity against Plasmodium falciparum infections among children from Busia-Eastern Uganda. Methods: In this study, we used archived samples of a birth cohort study (SBS-342) which was previously done in Busia. All samples from the birth cohort study were retrieved and screened for contamination and hemolysis. Dilution of the samples using buffer B was done in deep well plate and 50ul transferred to the Magpix plate and 50ul of the primary antigen coated with beads and diluted in buffer A was then added. This mixture was then incubated for 90 minutes and magnetized and washed after which a secondary antibody (Ab) was introduced and incubated for 60 minutes, magnetized and washed and 20ul of tertiary conjugated Ab was then added (labelled with fluorescence dye). This mixture was then washed and 100ul of plain PBS added and transferred to the Magpix machine for acquisition of Median Fluorescence Intensity. The Analysis of Variance and regression plotting were done using STATA ver 14.0 and graph pad prism respectively. Results: IgG2 was most abundant in cord blood, merozoite surface antigens elicited the most antibody response and infected RBCs antigens elicited least; gestational malaria prevalence significantly reduced antibody expression in cord blood against signature antigens and so was placental malaria, DP use significantly affected MSP119 anti IgG expression. The concentration of different IgG subtypes (IgG1, IgG2, IgG3 and IgG4) in cord blood played little or no role in protecting children against Plasmodium falciparum infection in the first birth year of children born to mothers in Busia a malaria endemic area. Conclusion: IgG subtypes most transferred to the fetus did not provide immune protection against plasmodium falciparum infection to children in the first birth year. Placental and gestational malaria are associated with reduced concentration of IgG subtypes in cord blood.