Expression of Properdin, the positive regulator of the Complement Alternative Pathway, at the fetal-maternal interface in Preeclampsia

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Introduction: Aberrant complement activation can cause damage to newly formed fetal-derived structures and excessive inflammatory response at the feto-maternal interface, contributing to pregnancy-related complications, including preeclampsia (PE), which is one of the most severe pathologies in new-borns. Properdin is the only known positive regulator of the complement alternative pathway, as it stabilizes the inherently labile C3bBb complex and amplifies its activity. This study describes the presence of properdin in PE and investigates its role in the pathogenesis. Methods: We examined the distribution and expression of properdin at both the transcript and protein levels in term placental tissue, serum, placental syncytiotrophoblast microvesicles (STBMs), and circulating placental exosomes from PE women compared to healthy mothers, using RT-qPCR, western blot, immunohistochemistry, transmission electron microscopy (TEM), and immunofluorescence. To link properdin levels with alternative pathway complement factors, we also assessed the expression of C3 and C5. Results: PE placentae showed significantly higher properdin, C3 and C5 at transcript as well as protein levels compared to healthy placentae. Conversely, properdin levels in serum, STBMs, and circulating placental exosomes were lower in PE compared to healthy pregnancies. Immunohistochemical analysis revealed properdin distribution throughout the PE placentae, with higher concentrations at the syncytial knots containing pyknotic nuclei were observed via TEM, along with elevated levels of cleaved caspase 3. Discussion: Thus, properdin was significantly upregulated in the PE placentae, along with C3 and C5, and might be associated with the apoptotic nuclei inside syncytial knots. This evidence suggests that properdin may trigger complement-mediated damage to the placental barrier, exacerbating the development of PE placentae.

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