Placental expression of alpha2,6-linked sialic acid is upregulated in malaria

Abstract

In Africa, approximately 25 million pregnant women are at risk of Plasmodium falciparum infection each year, one in four has evidence of placental involvement and up to half of these may be associated with low birth weight outcomes. In infected pregnant women, the placenta is an ideal site for the accumulation of the parasites, and this reduces in extent in subsequent pregnancies. Recent data indicate that terminal alpha2,3 sialic acid-dependent routes are central to the efficient invasion of erythrocytes with P. falciparum, however, the role in placental malaria of sialylated, or other glycoconjugates, on syncytiotrophoblast has not previously been assessed. Placental biopsies from Zambian women showed the Neu5Ac(alpha2,6)Gal/GalNAc sequences bound by the lectin from Sambucus nigra (SNA-1) to have greatly increased expression on microvillous membranes in samples with chronic P. falciparum infection showing, by electronic image analysis, a significant trend (p=0.002) compared to samples with past or no infection. This suggests a specific placental membrane response to falciparum malaria. Expression of alpha2,6-linked sialic acid, demonstrated by the binding of SNA-1, has been associated with intercellular repulsion in tissues from patients with cancer, and such repulsion resulting from increased alpha2,6 sialylation of chorionic villi could influence intervillous placental parasite density. Sialic acid expression should be examined in placental malaria to identify if this is a malaria-specific phenomenon, and to determine its relation to placental inflammation and pregnancy outcomes.