Natural immune response involving anti-endothelial cell antibodies in normal and lupus pregnancy.

Abstract

To determine whether immunoglobulins with affinity for the vascular endothelium displayed any distinguishing behavior during normal and systemic lupus erythematosus (SLE) pregnancy. We also attempted to verify whether isotype expression of anti-endothelial cell antibodies (AECA) would have any predictive value for pregnancy outcome. Sera from 38 pregnant patients with SLE, 68 normal pregnant women, and 84 nonpregnant healthy controls were studied. IgM- and IgG-AECA were determined by cellular enzyme-linked immunosorbent assay using fixed cultured human umbilical vein endothelial cells. A significantly higher level of IgM-AECA was found during normal pregnancy compared with that in healthy nonpregnant controls (mean +/- SD 39 +/- 12% versus 21 +/- 12%; P < 0.0001). Most pregnant patients with SLE did not have increased titers of IgM-AECA, but instead had levels similar to those found in healthy nonpregnant controls (23 +/- 12%; P not significant). The lowest levels of IgM-AECA in lupus pregnancy were associated with preeclampsia (odds ratio 16, P < 0.005). Conversely, IgG-AECA levels were significantly higher in the serum of normal pregnant women and pregnant SLE patients than in the serum of healthy nonpregnant controls (24 +/- 7% and 24 +/- 14% versus 9 +/- 7%; P < 0.0001). Our results indicate that an active immune response occurs during pregnancy. This response involves increased activity of AECA, suggesting a role of autoantibodies as a possible contributing factor toward fetal tolerance. Our observations further indicate that impaired immune regulation, such as diminished levels of serum IgM-AECA detected in SLE patients, might contribute to the impaired reproductive function commonly found in SLE.