Effects of anti-β2-GPI antibodies on cytokine production in normal first-trimester trophoblast cells.

Aim: The anti-β2-GPI antibody (aβ2-GPIAb) has been detected in recurrent fetal loss with strong pathogenic activity. The effects of aβ2-GPIAb on cytokine production and aβ2-GPIAb binding sites in first-trimester trophoblast cells were evaluated.

Methods: First-trimester trophoblast cells were cultured in 24-well tissue culture plates with immunoglobulin G (IgG) obtained from aβ2-GPIAb-positive and aβ2-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 aβ2-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.

Results: The production of cytokines, such as interleukin-6 and interleukin-8, increased more in response to aβ2-GPIAb-positive IgG than to aβ2-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.

Conclusion: We suspect that aβ2-GPIAb might increase cytokine production by binding to TLR2 or TLR4. The increased cytokine production in response to aβ2-GPIAb might play a role in the increased inflammatory response in the placenta.