Effects of anti-β2-glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line

• Published in: The journal of obstetrics and gynaecology research Vol. 37; no. 8; pp. 1076 - 1083
• Main Authors: Ichikawa, Go, Yamamoto, Tatsuo, Chishima, Fumihisa, Nakamura, Akikazu, Kuno, Souichirou, Murase, Takayuki, Suzuki, Manami
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01-08-2011
• Subjects: Abortion, Habitual - immunology; Abortion, Habitual - metabolism; Adult; anti-β2-glycoprotein I antibody; Autoantibodies - analysis; Autoantibodies - isolation & purification; Autoantibodies - metabolism; beta 2-Glycoprotein I - antagonists & inhibitors; beta 2-Glycoprotein I - physiology; Cell Line, Tumor; Choriocarcinoma - metabolism; choriocarcinoma cell; Down-Regulation; Female; Humans; Placenta Growth Factor; Pregnancy Proteins - blood; Pregnancy Proteins - metabolism; soluble vascular endothelial growth factor receptor-1; Trophoblasts - metabolism; vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascular Endothelial Growth Factors - blood; Vascular Endothelial Growth Factors - metabolism; Young Adult
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/j.1447-0756.2010.01490.x

Aim:  Anti‐β2‐glycoprotein I (anti‐β2‐GPI) antibody has been detected in cases of recurrent abortion and intrauterine death. Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) are growth factors that accelerate villous proliferation. Soluble VEGF receptor‐1 (sVEGFR1) is a soluble receptor for PlGF and suppresses the function of PlGF. In order to study the pathological mechanism of anti‐β2‐GPI antibody, we evaluated the effects of anti‐β2‐GPI antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cells.
Methods:  The sera were taken from six anti‐β2‐GPI antibody‐positive and six anti‐β2‐GPI antibody‐negative patients with recurrent miscarriages. Choriocarcinoma cells (JEG‐3) were cultured in 24‐well plates. After each serum and isolated immunoglobulin G (IgG) were added to the culture medium, the PlGF, VEGF and sVEGFR1 in the culture medium were measured by ELISA 24 h later. When the isolated IgG was added to culture medium, only the levels of PlGF were measured.
Results:  The anti‐β2‐GPI antibody‐positive sera and isolated IgG significantly suppressed the production of PlGF from JEG‐3 cells more strongly than the anti‐β2‐GPI antibody‐negative sera. The suppressive effects were not changed by serum inactivation. There was no significant difference in the values of the XTT assay and the production of VEGF and sVEGFR1 between the antibody‐positive and antibody‐negative sera.
Conclusions:  Anti‐β2‐GPI antibody‐positive sera and IgG suppress the production of PlGF from JEG‐3 cells. We suggest that the anti‐β2‐GPI antibodies may suppress PlGF production from trophoblasts and cause the failure of placenta formation and function.