Antiphospholipid antibody-induced trophoblast responses are differentially modulated by viral dsRNA and viral ssRNA.

PROBLEM: Women with antiphospholipid antibodies (aPL) are at increased risk for pregnancy loss and preeclampsia. aPL target the trophoblast and induce a pro-inflammatory, anti-angiogenic and anti-migratory profile. Since infection during pregnancy can increase the risk for preeclampsia, a viral infection could further increase this in women with aPL. The goal of this study was to characterize the effect of viral components on trophoblast responses to aPL. METHOD OF STUDY: A human first trimester trophoblast cell line was treated with or without aPL or control IgG in the presence of media, viral dsRNA or viral ssRNA. Supernatants were measured for inflammatory IL-1ß and IL-8; inflammasome-associated uric acid and caspase-1 activity; and anti-angiogenic sFlt-1. Trophoblast migration was measured using a two-chamber assay. RESULTS: Viral dsRNA augmented aPL-induced trophoblast caspase-1 activity, and IL-1ß and IL-8 secretion in an additive manner. Viral ssRNA inhibited aPL-induced uric acid, IL-1ß and sFlt-1 secretion, and further exacerbated aPL-inhibition of trophoblast migration. CONCLUSION: While viral ssRNA may have some protective effects on aPL-induced inflammation and anti-angiogenic responses, viral dsRNA exacerbated aPL-mediated inflammation and viral ssRNA further limited cell migration, which could prove detrimental to placentation. Thus, viral infections may contribute to adverse pregnancy outcomes in women with aPL.