Biological Basis of Fetoplacental Antigenic Determinants in the Induction of the Antiphospholipid Antibody Syndrome and Recurrent Pregnancy Loss

Abstract

We have reported autoimmune serological abnormalities in women with recurrent spontaneous abortions (RSAs).' Incidences of anti-phospholipid antibodies and antinuclear antibodies were significantly increased with each additional pregnancy loss in these women.* This was not seen in healthy, normal multiparous women. We also reported that 42% of women with three or more RSAs who were antiphospholipid antibody ( M A ) negative before the pregnancy became APA positive at the time of mi~carriage.~ Phospholipids are integral components of placental villous membrane, and there is evidence that trophoblastic antigenic stimuli during pregnancy may induce the production of various autoantibodies including antiphospholipid antibodies in failing pregnancies: In this study, we prospectively analyzed women with three or more RSAs and normal healthy women entering a pregnancy for autoantibodies at each trimester of pregnancy including cord blood samples.Thirty-one normal, healthy women with no history of RSAs who received antenatal care at Department of Obstetrics and Gynecology, Hospital Infantil in Bogota, Columbia and 32 women with three or more RSAs who registered at Reproductive Medicine, University of Health S c i e n c e f i e Chicago Medical School were investigated consecutively during the index pregnancy. All normal women were analyzed for IgG antibodies to six phospholipid epitopes, DNA, and histone at each trimester of pregnancy. Cord blood was also analyzed. Women with RSAs, IgM, and IgG APA were followed during pregnancy and at delivery or at the time of a repeated abortion. Titers of APAs were measured by ELISA as previously reported.'We report: (1) In women with a normal pregnancy, there is no APA positivity during pregnancy including cord blood (FIG. 1); (2) 6.5% of normal pregnant women demonstrated low positive ANA during pregnancy; (3) no one developed lupus anticoagulant during the index pregnancy; (4) 3.2% of normal pregnant women demonstrated IgG single-stranded DNA and 3.2% IgG double-stranded DNA. No one developed IgG antibodies to histone; ( 5 ) increased parity in women with a normal 242

Diagnosis and management of non-criteria obstetric antiphospholipid syndrome

“…The interval of 12 weeks between aPL tests, which appears to be an arbitrary interval, to establish persistence of aPL, may be challenging to achieve in the nonpregnant state in women with obstetric morbidity. This may be compounded by findings suggesting that aPL testing may not be representative during pregnancy (55,56).…”