title: Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, in which pre-eclampsia and other complications developed. We performed standard histopathological placental review and quantified neutrophils and neutrophil extracellular traps (NETs) in the intervillous space, given the recognised association of NETs with lupus, APS and pre-eclampsia.
  
  
  METHODS
  Pre-eclampsia, SLE and control placentas were scored for histological features, and neutrophils were quantified on H&E and immunohistochemical staining for the granular protein myeloperoxidase. NETs were identified by extracellular myeloperoxidase staining in the setting of decondensed nuclei. Non-parametric analysis was used to evaluate differences in netting and intact neutrophils between groups, with Kruskal-Wallis testing for associations between histological findings and neutrophils.
  
  
  RESULTS
  Placentas were evaluated from 35 pregnancies: 10 controls, 11 pre-eclampsia, 4 SLE+pre-eclampsia and 10 SLE, including one complicated by catastrophic APS and one complicated by hepatic and splenic vein thromboses during pregnancy. Intrauterine growth restriction and oligohydramnios were observed in lupus cases but not controls. Significantly more NETs were found infiltrating placental intervillous spaces in pre-eclampsia, SLE+pre-eclampsia and all 10 SLE non-pre-eclampsia cases. The ratio of NETs to total neutrophils was significantly increased in all case groups compared with controls. When present, NETs were associated with maternal vasculitis, laminar decidual necrosis, maternal-fetal interface haemorrhage and non-occlusive fetal thrombotic vasculopathy.
  
  
  CONCLUSIONS
  In this pilot study of placental tissue from lupus pregnancies, outcomes were more complicated, particularly if associated with APS. Placental tissue revealed marked inflammatory and vascular changes that were essentially indistinguishable from placental tissue of pre-eclampsia pregnancies.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine,University of Michigan, Ann Arbor, Michigan, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Marder
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Knight
authors.affiliation: Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, Maryland , USA.
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
authors.affiliation: Division of Rheumatology, Department of Internal Medicine,University of Michigan, Ann Arbor, Michigan, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA; Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: O'Dell
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Padmanabhan
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lieberman
keywords: Autoimmune Diseases; Systemic Lupus Erythematosus; pregnancy