Abstract
To compare immune cell subsets and interferon (IFN) expression in placentas from patients with systemic lupus erythematosus (SLE), primary Sjögren's disease (pSjD), antiphospholipid syndrome (APS), healthy controls (HC) and of women with adverse pregnancy outcomes (APO) without these systemic rheumatic diseases (SRD). Placenta biopsies from HC, SLE, pSjD, APS, and patients with fetal growth restriction (FGR), spontaneous preterm birth (PTB), or FGR and preeclampsia (FGR/PE) attended between 2008 and 2022 were recovered from the pathology biobank of the University Medical Center Groningen. Clinical characteristics and APO were retrieved from medical records. Immunohistochemistry was performed for Myxovirus resistance protein 1 (MxA), CD3, CD20, CD56, CD68, CD123, and Foxp3. The proportion of positive cells was established using an automated detection classifier, while MxA expression was assessed semi/quantitatively discriminating between maternal (decidua) and fetal (villi) tissue. Finally, placental lesion classification was performed. Our study included placentas from 11 SLE, 4 pSjD, 8 APS, 4 PTB, 8 FGR, 8 FGR/PE patients and 11 HC. A high rate of APO (70%) was identified in SRD patients. Patients with SRD had a higher macrophage (CD68+) count in decidua and villi than HC, but no differences were observed in T (CD3+), B (CD20+), NK (CD56+) and T regulatory (Foxp3+) cell count. No plasmacytoid dendritic cells (CD123+) were identified. Furthermore, patients with these SRD had higher MxA values than HC in villi but not in decidua. SLE, pSjD and APS patients have an increased macrophage count and interferon upregulation in the placenta compared to HC. Therefore, a pro-inflammatory environment might be key inducing placental dysfunction, which may lead to subsequent APO development.