Biological mechanisms in blood and placenta during pregnancy in systemic lupus erythematosus

Abstract

The overall aim of this thesis was to investigate immunological and biological mech-anisms in blood and placenta during pregnancy in women with systemic lupus erythe-matosus (SLE), in order to improve understanding of the increased risk of maternal and fetal complications. Pregnant women with SLE and healthy pregnant controls were longitudinally fol-lowed within the SLE-Placenta cohort. Blood samples were collected in each trimester and during the late postpartum period, as well as placental intervillous blood and um-bilical cord blood at delivery. Placental tissue was also collected at delivery. Circulating immune cell subsets were analyzed by flow cytometry. Plasma protein concentrations were quantified using ELISA, and IFNα levels were measured with Simoa. In a sub-group, plasma proteomic profiling and gene expression analyses in PBMCs and placen-tal tissue were performed. Paper I demonstrated increased granulocyte activation and elevated proportions of low-density granulocytes (LDGs) in SLE pregnancies, associated with antiphospholipid antibody positivity and shorter pregnancy duration, together with consistently elevated IFNα levels. Paper II showed persistently reduced lymphocyte subset counts in women with SLE during pregnancy, with differential associations to autoantibody profiles and IFNα levels. In Paper III, circulating BAFF levels were increased in SLE pregnancies and associated with reduced B cell numbers, autoantibody positivity, and shorter preg-nancy duration. In addition, BAFF and IFNα were enriched in placental blood. Paper IV identified the angiogenesis-related proteins endostatin and angiogenin as being as-sociated with pre-eclampsia in SLE. Endostatin was persistently elevated and signifi-cantly enriched in placental blood compared with peripheral circulation. In conclusion, pregnancy in SLE is characterized by prominent disease-related in-flammatory activation together with insufficient pregnancy-related immune adaptation, which may negatively affect pregnancy progression and placental development. More-over, an imbalance in angiogenesis-related factors, particularly endostatin, suggests un-derlying placental dysfunction in SLE and may contribute to the increased risk of pre-eclampsia. Further mechanistic studies are needed to clarify these processes.