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 despite the presence of significant anticardiolipin antibody (ACA) activity. We evaluated whether a correlation exists between ACA activity and the degree of fetal resorption in murine pregnancy and also determined whether pooled IgG from multiple ACA-positive patients increases the likelihood of fetal resorption compared with injection of single-donor IgG.Methods: Affinity chromatography followed by anisotropic ultrafiltration was used to extract and concentrate IgG from individual serum samples with and without ACA activity (ACA-positive IgG activity, 35-85 GPL versus ACA-negative IgG activity, <1 GPL) and from pooled aliquots derived from the same sera. On Day 8 of gestation, pregnant mice randomly received intraperitoneal injections of ACA-positive or ACA-negative, purified IgG (15 mg/mouse) or saline (1 ml). Laparotomies were performed on day 15, and uteri were harvested for gross evaluation and histologic study. Rates of fetal resorption were derived for each murine pregnancy (resorbed fetuses/resorbed fetuses + live pups) and compared between experimental groups.Results: A significant increase in fetal resorption rate was observed in ACA-positive IgG-treated animals (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 pregnancies did not correlate with initial ACA activity of the whole serum or with antibody activity measured in the purified, concentrated IgG preparations. A comparison of fetal resorption between single donor ACA-positive IgG and pooled ACA-positive IgG revealed similar rates of fetal resorption (20.5 versus 17.9%, respectively) but a lower mean birth weight among non-resorbed pups in the single-donor IgG-treated pregnancies (340 versus 430 mg; P = 0.05).Conclusions: Although greater murine fetal resorption resulted from ACA-positive IgG administration compared with ACA-negative IgG or saline injection, marked variability in pregnancy outcome was observed among ACA-positive animals. These differences were not attributable to initial antibody activity in whole serum or to activity associated with the purified immunoglobulins. Combining multiple ACA-positive sera did not augment the rate of fetal resorption.
Silver
RK
Perinatal Research Group, Departments of Obstetrics & Gynecology, Pediatrics, and Pathology, Evanston Hospital, Northwestern University Medical School, Evanston, Illinois
Russell
TL
Brodin
AG
Check
IJ
Helfand
BT
Caplan
MS