Human extravillous trophoblasts bind but do not internalize antiphospholipid antibodies

Area of Science:

• Reproductive immunology
• Cell biology
• Obstetrics

Background:

• Obstetric morbidity in antiphospholipid antibody (aPL) positive women may stem from aPL effects on placental cells.
• aPLs may affect syncytiotrophoblasts via internalization mediated by Low-density lipoprotein receptor (LDLR) family members and β2 glycoprotein I.

Purpose of the Study:

• To investigate if aPL internalization is a mechanism by which aPLs adversely affect extravillous trophoblasts.

Main Methods:

• Fluorescently-labeled monoclonal aPLs were incubated with first-trimester extravillous trophoblast outgrowths.
• Microscopy was used for visualization.
• Subcellular expression of β2 glycoprotein I and LDLR family members was assessed via immunocytochemistry.

Main Results:

• Monoclonal aPLs were not internalized by extravillous trophoblasts.
• Extravillous trophoblasts expressed LDLR family members intracellularly.
• aPL IIC5 bound to the extravillous trophoblast surface, mirroring extracellular β2 glycoprotein I expression.

Conclusions:

• Antiphospholipid antibody mechanisms differ between extravillous trophoblasts and syncytiotrophoblasts.
• aPL interaction with extravillous trophoblast surface receptors, potentially involving β2 glycoprotein I, may trigger intracellular signaling.