Hydroxychloroquine Prevents Antiphospholipid Antibody-Induced Inhibition Of Trophoblast Migration

HYDROXYCHLOROQUINE PREVENTS ANTIPHOSPHOLIPID ANTIBODYINDUCED INHIBITION OF TROPHOBLAST MIGRATION Women with antiphospholipid syndrome (APS) are at high risk of recurrent pregnancy complications. Antiphospholipid antibodies (aPL) target the trophoblast by binding beta2glycoprotein I (β2GPI) and alter human first trimester trophoblast function by: triggering a pro-inflammatory cytokine response; modulating angiogenic factor secretion; and inhibiting cell migration. While patients with APS are often treated with hydroxychloroquine (HCQ), and it is safe to use during pregnancy, little is known about the effects of HCQ on aPL-associated adverse pregnancy outcomes. Therefore, the objective of this study was to test the hypothesis that HCQ prevents the effects of aPL on human first trimester trophoblast function. A human first trimester trophoblast cell line was treated with or without anti-human β2GPI monoclonal antibodies in the presence or absence of HCQ. Using ELISA, culture supernatants were analyzed for: proinflammatory cytokines IL-8 and IL-1β; pro-angiogenic factors VEGF and PlGF; antiangiogenic factors sFlt-1 and soluble Endoglin; pro-migratory cytokine IL-6; and tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2). Cell migration was measured using a colormetric two-chamber assay. The aPL-induced upregulation of trophoblast IL-8, IL-1β, PlGF, and sEndoglin secretion was not significantly altered by the presence of HCQ. The presence of HCQ partially, yet significantly, reversed the aPLinduced inhibition of trophoblast cell migration and secretion of pro-migratory cytokine IL-6. aPL-induced upregulation of trophoblast TIMP secretion appears to inhibit cell migration. HCQ was unable to completely prevent aPL-induced TIMP secretion, and this