Pregnancy outcomes in systemic autoimmune diseases

In systemic autoimmune diseases (SAD), the immune system attacks healthy cells in the body, generating a wide variety of symptoms from fatigue to life-threatening organ damage. Women with SAD such as systemic lupus erythematosus (SLE), primary Sjögren’s disease (pSjD) or antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes (APO) such as pregnancy loss, pregnancy induced hypertension, preeclampsia, preterm birth, fetal growth restriction or a small for gestational age newborn. In this thesis, we aimed to identify preconceptional risk factors and immunologic imbalances during pregnancy in women with SAD and determine their association with APO. Preconception risk factors for APO such as previous lupus nephritis, chronic hypertension, preconception active disease and secondary APS diagnosis were the most relevant in patients with SLE. Also, low complement C4 levels before pregnancy were associated with APO in patients with pSjD. Concerning immunological imbalances, we described high amounts of macrophages and interferon (a proinflammatory marker) in the placenta of patients with SAD and designed and started the Pregnancy Outcomes in Autoimmune Diseases: POAD study, a prospective cohort in the north of the Netherlands which follows women before and during pregnancy to further explore the immunologic imbalances in these patients. In the last part of this thesis, we discussed new insights into APS pathophysiology, highlighting the role of certain types of antibodies and the use of hydroxychloroquine as a treatment for obstetric complications such as preterm birth or pregnancy loss.