Background: Systemic lupus erythematosus (SLE) predominantly affects women of reproductive age, which means that many SLE patients wish to become pregnant. Unfortunately, up to 50% of women with SLE will experience pregnancy complications, such as pre-eclampsia, fetal growth restriction and preterm birth. Interestingly, this increased risk persists in subsequent pregnancies from the same father, whereas it decreases in healthy women due to the development of maternal-fetal tolerance. This suggests a failure of maternal-fetal tolerance in women with SLE, leading to their high risk of pregnancy complications. Understanding the mechanisms underlying this impaired immunological tolerance is crucial for improving prediction, prevention, and treatment of pregnancy complications in SLE. Maternal-fetal tolerance is established at the placental interface, which is in constant contact with maternal blood. Therefore, a key first step in understanding pregnancy complications in SLE is to characterize the peripheral blood immune cell subsets in pregnant women with SLE.

Objectives: To compare the composition of myeloid cells, B cells, and T cells in longitudinal blood samples from pregnant women with SLE, stratified by the presence or absence of pregnancy complications.

Methods: Peripheral blood mononuclear cells (PBMCs) were collected as part of the FaMaLE study, a prospective cohort including healthy women and women with SLE (meeting ACR1997, SLICC, and/or ACR/EULAR 2019 criteria) enrolled during the first trimester. Participants were followed throughout pregnancy, with blood samples obtained once per trimester (10–14, 20–24, and 30–34 weeks gestational age), within 48 hours prior to delivery, and 5–12 weeks postpartum. PBMCs were analyzed using three flow cytometry panels to assess myeloid, B cell, and T cell subsets.

Results: Interim analysis revealed no significant differences in the proportions of neutrophils, dendritic cells, or monocytes between women with and without complications. However, women who developed complications, particularly those with pre-eclampsia, exhibited a reduction in total B cells from the second trimester onwards compared to those with uncomplicated pregnancies. Further analysis indicated an increased proportion of activated and memory B cells, and a decrease in transitional B cells, in women with pre-eclampsia. Similar but less pronounced trends were observed in women with preterm birth, while women with SGA alone showed no major differences in B cell subsets.

No significant differences were observed in the overall percentage of T cells between groups. However, there was a trend toward reduced CD4+ T cells, a lower CD4/CD8 ratio, and a decreased proportion of naïve CD4+ T cells in women with complications, particularly in those with preterm birth.

Conclusions: Alterations in B and T cell composition are detectable early in pregnancy in women with SLE who subsequently develop pregnancy complications. These immunological changes may serve as early markers for the prediction of adverse pregnancy outcomes. Further studies in larger cohorts are warranted to validate these findings and to elucidate their functional significance.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.