Immune cell infiltrate at the utero-placental interface is altered in placenta accreta spectrum disorders

To characterize the immune cell infiltrate associated with maternal vascular remodeling in 12 cases of cesarean hysterectomy from women with placenta accreta spectrum (PAS) disorder.

Myometrial vessels were evaluated by hematoxylin and eosin and immunohistochemistry stains on tissue microarrays that included samples from the myometrium, deep to the implantation site. Vessels were quantified based on physiologic conversion and immune cell infiltrates. Placental bed biopsies from cases of repeat cesarean section, and decidual vessels from delivered non-PAS placentas were used as controls.

Immune cells, predominantly macrophages and T-cells, were present as a band along the placental-myometrial interface in PAS cases. However, within the myometrium, the infiltrate showed a perivascular accentuation. The infiltrates around and within vessel walls were composed of T-cells (CD3) and macrophages (CD68), with fewer NK (CD56), Treg (FoxP3) and rare B-cells (CD20). Plasma cells (CD138) were absent. The majority of vessels with immune cell infiltrates had undergone complete or partial physiologic conversion by trophoblast. However, a subset of unconverted vessels in the myometrium had a similar immune cell infiltration. Control blood vessels showed a similar pattern of leukocytes infiltration in the decidua and placental bed biopsies, but with a lower density.

Our findings suggest that myometrial vascular changes in PAS resemble the physiological changes of vessels noted in the implantation site of normal pregnancies. The presence of perivascular immune cell infiltrates in the absence of adjacent trophoblast suggests that the process may be initiated by paracrine effects rather than direct contact or endovascular growth of trophoblast.