ABSTRACT
AIM: Anti-ß2-glycoprotein I (anti-ß2-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-ß2-GPI antibody, we evaluated the effects of anti-ß2-GPI antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cells. METHODS: The sera were taken from six anti-ß2-GPI antibody-positive and six anti-ß2-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-ß2-GPI antibody-positive sera and isolated IgG significantly suppressed the production of PlGF from JEG-3 cells more strongly than the anti-ß2-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-ß2-GPI antibody-positive sera and IgG suppress the production of PlGF from JEG-3 cells. We suggest that the anti-ß2-GPI antibodies may suppress PlGF production from trophoblasts and cause the failure of placenta formation and function.
Subject(s)
Abortion, Habitual/immunology , Autoantibodies/metabolism , Pregnancy Proteins/metabolism , Trophoblasts/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factors/metabolism , beta 2-Glycoprotein I/antagonists & inhibitors , Abortion, Habitual/metabolism , Adult , Autoantibodies/analysis , Autoantibodies/isolation & purification , Cell Line, Tumor , Choriocarcinoma/metabolism , Down-Regulation , Female , Humans , Placenta Growth Factor , Pregnancy Proteins/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factors/blood , Young Adult , beta 2-Glycoprotein I/physiologyABSTRACT
UNLABELLED: In order to know the comlement activation, the changes of compliment were evaluated in recurrent abortion and pregnancy loss patients with antiphospholipid antibody (APA) positive. Serum samples were taken from 82 patients with more than 2 recurrent abortion patients and/or pregnancy loss. Fifty eight cases of 82 patients were APA and antinuclear antibody negative without autoimmune disease. Anticardiolipin antibody (ACA), anti CL/beta2-GPI antibody (CL/beta2-GPI) were measured using ELISA. Lupus anticoagulant (LAC) was measured using diluted RVVT. CH50 and C3 and C4 were measured as complements. The number of positive cases of ACA, CL/beta2-GPI, LAC was 23, 9 and 5 cases, respectively. RESULTS: The levels (mean+/-SD) of CH50, C3 and C4 in ACA positive and negative cases were 38.8+/-8.3 U/ml, 82.7+/-20.1 mg/dl, 18.5+/-5.7 mg/dl and 42.4+/-6.9 U/ml, 93.5+/-17.6 mg/dl, 21.1+/-4.6 mg/dl, respectively. The levels of CH50, C3 and C4 in positive cases were significantly lower than negatives. The levels of CH50, C3 and C4 in CL/beta2-GPI and LAC positive cases were also significantly lower than negatives. CONCLUSION: The comlement activation was demonstrated in recurrent abortion and pregnancy loss with antiphospholipid antibody positive.
