Anti–protein Z antibodies in women with pathologic pregnancies

Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enzyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti-protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti-protein Z antibodies were categorized in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti-protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.