VARIABILITY OF MURINE PREGNANCY OUTCOME RESULTING FROM PASSIVE-IMMUNIZATION WITH ANTICARDIOLIPIN ANTIBODY-POSITIVE IMMUNOGLOBULIN-G

Objective: Administration of purified human IgG from antiphospholipid syndrome patients has not consistently caused murine pregnancy loss de spite the presence of significant anticardiolipin antibody (ACA) activ ity. We evaluated whether a correlation exists between ACA activity an d the degree of fetal resorption in murine pregnancy and also determin ed whether pooled IgG from multiple ACA-positive patients increases th e likelihood of fetal resorption compared with injection of single-don or IgG. Methods: Affinity chromatography followed by anisotropic ultra filtration was used to extract and concentrate IgG from individual ser um samples with and without ACA activity (ACA-positive IgG activity, 3 5-85 GPL versus ACA-negative IgG activity, <1 GPL) and from pooled ali quots derived from the same sera. On Day 8 of gestation, pregnant mice randomly received intraperitoneal injections of ACA-positive or ACA-n egative, purified IgG (15 mg/mouse) or saline (1 ml). Laparotomies wer e performed on day 15, and uteri were harvested for gross evaluation a nd histologic study. Rates of fetal resorption were derived for each m urine pregnancy (resorbed fetuses/resorbed fetuses + live pups) and co mpared between experimental groups. Results: A significant increase in fetal resorption rate was observed in ACA-positive IgG-treated animal s (n = 19, 19.3%) compared with either ACA-negative (n = 5, 6.4%; P = 0.008) or saline-treated pregnancies (n = 8, 4.6%; P = 0.004). However , differences in resorption rates among the ACA-positive IgG-treated p regnancies did not correlate with initial ACA activity of the whole se rum or with antibody activity measured in the purified, concentrated I gG preparations. A comparison of fetal resorption between single donor ACA-positive IgG and pooled ACA-positive IgG revealed similar rates o f fetal resorption (20.5 versus 17.9%, respectively) but a lower mean birth weight among non-resorbed pups in the single-donor IgG-treated p regnancies (340 versus 430 mg; P = 0.05). Conclusions: Although greate r murine fetal resorption resulted from ACA-positive IgG administratio n compared with ACA-negative IgG or saline injection, marked variabili ty in pregnancy outcome was observed among ACA-positive animals. These differences were not attributable to initial antibody activity in who le serum or to activity associated with the purified immunoglobulins. Combining multiple ACA-positive sera did not augment the rate of fetal resorption.