Status: Funded - Open
Placental malaria and maternal-fetal microchimerism
Whitney Harrington, M.D., Ph.D.
BACKGROUND: 125 million pregnant women are at risk of malaria each year, resulting in poor outcomes for the fetus, neonate, and infant, and an estimated 1,300 children under five die of malaria each day. The determinants of malaria susceptibility in pregnancy and infancy are largely unknown but may include microchimerism (Mc), a form of non-Mendelian maternal heritability. Bidirectional maternal-fetal exchange during pregnancy leads to maternal Mc, induction of fetal regulatory T cells to maternal antigens, and durable maternal-specific tolerance.
GAP: The effect of malaria infection during pregnancy on Mc has not yet been explored. However, Mc may be a potential mechanism for the association between placental malaria (PM) and malaria susceptibility during infancy via induction of fetal alloimmune tolerance to antigens presented by microchimeric maternal antigen presenting cells.
HYPOTHESIS: We hypothesize that PM, with its associated damage to the trophoblast barrier, increases the prevalence and level of maternal Mc.
METHODS: We will use a cross-sectional design comparing women with and without PM and their children, matched for demographic factors and derived from a larger, pre-established birth cohort from Muheza, Tanzania. Women and their infants will be genotyped at polymorphic loci to determine a discordant marker, and Mc will be investigated in infant samples using a validated quantitative PCR protocol.
IMPACT: If successful, we will next investigate the association between Mc and susceptibility to malaria during infancy, which may lead to modulation of maternal immune influences experienced in utero as a new strategy to prevent malaria during infancy.
Fred Hutchinson Cancer Research Center