Blood immunomonitoring uncovers pregnancy-induced immune programs and their dysregulation in lupus pregnancy destined for complications

Systemic lupus erythematosus carries increased risk of pregnancy complications. To understand the underlying molecular mechanisms, we characterized the blood transcriptome of lupus patients and healthy controls during pregnancy and postpartum and performed multicolor flow-cytometry in a subset. We also followed healthy women undergoing assisted reproductive technology, allowing for analysis around embryo implantation. A striking and sustained down modulation of two lupus-related signatures, interferon and plasma cells, takes place during healthy pregnancy. These changes appear immediately post embryo implantation and are mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early upregulation of neutrophil signatures and expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as ICOS+ CD4+ T cell counts. Thus, healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and failure to do so is associated with adverse outcomes. 512 total samples; 325 SLE samples; 187 without SLE. Samples were taken under the following conditions: not pregnant or NP, <16 wks pregnant, 16-23 weeks pregnant, 24-31 weeks pregnant, 32-40 weeks pregnant, post-partum or PP. Description of sample characteristics: GRP_P_TP; Disease group, Pregnancy/non-pregnancy, timepoint, a variable used for mixed model GA_AT_COLLECTION; Gestational age at collection (week) GA_at_end_of_Pregnancy; Gestational age at the end of pregnancy (week) SLE; yes=1, no=0 aPL; Antiphospholipid antibodies yes=1, no=0 LAC; Lupus Anticoagulant yes=1, no=0 TP; time point [1: <16 weeks of gestation (WG); 2: 16-23 WG; 3: 24-31 WG; 4: 32-40 WG, and between 8 and 20 weeks postpartum (5)] PE; Preeclampsia yes=1, no=0 If_PE_before_or_after_36_weeks; If the patient had preeclampsia, before or after 36 WG FD; Fetal death NND; Neonatal death PL_Insuff; preterm delivery <36 weeks because of placental insufficiency IUGR; Intrauterine growth restriction SGA; small-for-gestational-age neonate