Maternal Infection with Schistosoma japonicum Induces a Profibrotic Response in Neonates

Abstract

ABSTRACTThe global burden of schistosomiasis is significant, with fibrosis a major associated morbidity and the primary cause of mortality. We have previously shown that schistosomiasis during pregnancy upregulates proinflammatory cytokines in the cord blood. In this study, we extend these findings to include a large panel of fibrosis-associated markers. We developed a multiplex bead-based assay to measure the levels of 35 proteins associated with fibrosis. Cord blood from 109 neonates born to mothers residing in an area ofSchistosoma japonicumendemicity was assessed for these molecules. Ten mediators were elevated in the cord blood from schistosome-infected pregnancies, including insulin-like growth factor 1 (IGF-1), tumor growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), procollagen I carboxy-terminal propeptide (PICP), amino-telopeptide of type 1 collagen (ICTP), collagen VI, desmosine, matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 1 (TIMP-1), and TIMP-4. Many of these were also positively correlated with preterm birth (PICP, ICTP, MMP-2, TGF-β1, desmosine, CTGF, TIMP-1). In addition, birth weight was 168 g lower for infants with detectable levels of CTGF than for those with CTGF levels below the level of detection. Maternal schistosomiasis results in upregulation of fibrosis-associated proteins in the cord blood of the neonate, a subset of which are also associated with adverse birth outcomes. As the first report of fibrosis-associated molecules altered in the newborn of infected mothers, this study has broad implications for the health of the fetus, stretching from gestation to adulthood.