Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies

Abstract

Objective: Studies that use a murine model of antiphospholipid syndrome have demonstrated a critical role for complement activation that leads to fetal and placental injury in the presence of antiphospholipid antibodies (APAs). We examined the placentas of patients with APAs to demonstrate a similar association with tissue injury in humans.

Study design: Immunohistochemical analyses with the use of antibodies to the complement products C4d, C3b, and C5b-9 were performed on paraffin-embedded tissue sections of placentas from 47 patients with APAs and 23 normal control patients.

Results: We found evidence of increased complement deposition in the trophoblast cytoplasm (C4d and C3b), trophoblastic cell and basement membrane (C4d), and extravillous trophoblasts (C4d) of patients with APAs, compared with control patients. We report a correlation between placental pathologic features and complement deposition (C4d) in the trophoblastic cytoplasm, cell membrane, and basement membrane.

Conclusion: These findings are consistent with murine studies that implicate complement as a critical factor in the fetal tissue injury observed in antiphospholipid syndrome.

Figures

FIGURE 1. Villous trophoblast cytoplasm

Strong immunohistochemical reactivity to C4d in the villous trophoblast (original magnification, ×40).

FIGURE 2. Villous trophoblast cell and basement membranes

Strong immunohistochemical reactivity to C4d in the cell membrane and basement membrane of the villous trophoblast (original magnification, ×40).

FIGURE 3. Extravillous trophoblasts of the basal plate

Individual extravillous trophoblasts are present throughout the decidua and show strong immunohistochemical reactivity to C4d (original magnification, ×40). V, chorionic villi of the basal plate; D, decidua.