Effects of anti-2-GPI antibodies on cytokine production in normal first-trimester trophoblast cells

AimThe anti-2-GPI antibody (a2-GPIAb) has been detected in recurrent fetal loss with strong pathogenic activity. The effects of a2-GPIAb on cytokine production and a2-GPIAb binding sites in first-trimester trophoblast cells were evaluated. MethodsFirst-trimester trophoblast cells were cultured in 24-well tissue culture plates with immunoglobulin G (IgG) obtained from a2-GPIAb-positive and a2-GPIAb-negative serum. Cytokines in the cultured supernatant were measured using the suspension array system and enzyme-linked immunosorbent assays. To identify potential binding sites for a2-GPIAb, such as toll-like receptors (TLR) 2 or TLR4, we used mouse monoclonal anti-TLR2 and/or anti-TLR4 antibodies to inhibit TLR and then measured cytokine production. ResultsThe production of cytokines, such as interleukin-6 and interleukin-8, increased more in response to a2-GPIAb-positive IgG than to a2-GPIAb-negative IgG in trophoblast cells. The secretion of cytokines from trophoblast cells decreased when the TLR were blocked with mouse monoclonal anti-TLR2 and anti-TLR4 antibodies. ConclusionWe suspect that a2-GPIAb might increase cytokine production by binding to TLR2 or TLR4. The increased cytokine production in response to a2-GPIAb might play a role in the increased inflammatory response in the placenta.