Anticardiolipin Antibodies in Patients With Pregnancy Loss Induce Factor Xa Production in the Presence of (β2-Glycoprotein I

PROBLEM : Anticardiolipin antibodies (aCL) are commonly associated with recurrent pregnancy loss, though the mechanism is uncertain. Some investigators have indicated that aCL may be directed at a complex made up of cardiolipin and a blood anticoagulant, β2-glycoprotein I (β2GPI). We therefore investigated the effects of β2GPI-dependent aCL IgG enriched fractions, isolated from sera of patients with pregnancy losses, on blood coagulation. METHOD : β2GPI-dependent aCL were prepared from sera of three women with second trimester pregnancy losses, by cardiolipin affinity column chromography, following by anti-β2GPI affinity column chromatography. The effects of β2GPI and β2GPI-dependent aCL on the activation of factor X in vitro were examined. RESULTS : β2GPI inhibited the activation of factor X and β2GPI-dependent aCL blocked this inhibitory effect in a dose dependent manner. CONCLUSION : These results imply the possibility of β2GPI-dependent aCL induce hypercoagulation or thrombus by blocking the inhibitory effect of β2GPI on activation of factor X, which may result in pregnancy loss.     

Clinical Significance of Anti-GM3 Antibodies in Recurrent Pregnancy Loss With Elevated Level of Antiphospholipid Antibodies

PROBLEM : The ganglioside-GM3 neutralizes the reactivity of antiphospholipid antibodies (APLs) to phospholipids in vitro. The question of whether anti-GM3 antibodies might exert influence in APLs-positive recurrent pregnancy loss patients who are undergoing prednisolone and aspirin (PSL/ASA) treatment was investigated. METHOD : The anti-GM3 antibody assay of sera was accomplished by ELISA. Sera of 56 patients with recurrent pregnancy loss, including 30 APLs-positive cases given PSL/ASA treatment, were examined. RESULTS : Patients positive for IgG or IgM type anti-GM3 antibodies constituted 13/30 (43%) of the APLs-positive group as compared with only 2/26 (8%) of those who were negative (P<0.01). In pregnant women with APLs-positive treated with PSL/ASA, live births occurred in only 6/13 (46%) patients with detectable anti-GM3 antibodies, while in 16/17 (94%) who tested negative for anti-GM3 antibodies (P<0.01). CONCLUSIONS : This observation suggests the possibility that presence of anti-GM3 antibodies may be an indicator for determining the prognosis in recurrent pregnancy loss with elevated level of APLs.     

Immunotoxicological Insignificance of Fenitrothion in Mice and Rats

Fenitrothion was administered orally to mice or rats in dailydoses of up to of the LD50 for 14 days, and numbers of splenic plaque-forming cells against sheep redblood cells (SRBC-PFC), one of the most common immune parameters,were measured. Splenic SRBC-PFC number was suppressed by fenitrothiononly in rats which received 30 mg/kg body weight (bw) of thecompound. Other immune parameters, including the arthus reaction,delayed-type hypersensitivity, and activities of macrophagesand natural killer cells in rats, were not influenced by fenitrothion.Adrenal hyperfunction manifesting as increased organ weightand elevated plasma corticosterone level was noted along withstrong cholinergic signs in rats which received 30 mg/kg bwof fenitrothion. At lower doses such as 3 or 0.3 mg/kg bw offenitrothion, rats had no strong cholinergic signs, adrenalhyperfunction, or evidence of immunosuppression despite significantsuppression of systemic cholinesterase (ChE) activities. Inmice, no suppression of SRBC-PFC number or mixed lymphocytereaction was noted even at the highest dose (40 mg/kg bw) offenitrothion, at which significant suppression of systemic ChEactivities but no cholinergic signs were noted. These findingsstrongly suggest that the im-munosuppressive effect of fenitrothionnoted in rats was due to systemic, potent cholinergic stressand that fenitrothion has no immunotoxicity in mice and rats.