Interferon, complement and immune cell imbalances in pregnant women with systemic autoimmune diseases

Systemic lupus erythematosus (SLE), primary Sjögren*s syndrome (pSS) and
antiphospholipid syndrome (APS) are systemic autoimmune diseases with a strong
female predominance and are associated with adverse pregnancy outcomes. SLE and
pSS are characterized by chronic immune cell activation. Throughout pregnancy,
the maternal immune system must tolerate a semi-allogenic fetus. Multiple and
specific immune adaptations are known to be involved in this immune tolerance,
and maternal immune activation is associated with pregnancy complications as
preterm birth, preeclampsia, low birth weight, recurrent pregnancy losses, and
fetal growth restriction (FGR) (1). The underlying causes of such
placenta-related complications in SLE, pSS and APS patients have not been fully
elucidated.

Overall aim
Identify immunologic imbalances, with a focus on IFN, NETs, complement and
lymphocyte subsets during pregnancy in women with systemic autoimmune diseases.

Hypothesis
We hypothesize that increased IFN activation and NET formation in patients with
SLE, pSS and APS result in a more inflammatory state of the maternal immune
system resulting in complement activation and altered distribution of immune
cell subsets in the placenta and maternal peripheral blood.

Objectives
- To assess IFN upregulation in maternal and cord blood and placental tissue
during pregnancy in women with SLE, pSS and APS

- To establish the amount of (autoantibody-induced) NET formation using serum
of pregnant patients with SLE, pSS and APS

- Describe alterations in blood and placental immune cell composition during
pregnancy in women with SLE, pSS and APS

- Identify the association between IFN upregulation, NETs formation, levels of
complement and lymphocyte subsets with adverse pregnancy outcomes in women with
SLE, pSS and APS

This is a longitudinal follow-up study of pregnant SLE, pSS, and APS patients.
Data, clinical as well as biological, will be collected prospectively. The data
will be compared to pregnant patients with rheumatoid artritis (RA) as disease
control and to healthy pregnant women. As part of standard care, these patients
will be followed at the department of Gynaecology and Obstetrics and at the
department of Rheumatology and Clinical Immunology during their pregnancy.
Visits will take place before pregnancy, during each trimester and at delivery.

All patients will receive standard care and treatment during follow up.
Procedures that will be solely done for research purposes are: extra blood
withdrawal during each trimester and at delivery. Also cord blood will be taken
and placental tissue will be collected at delivery. All study visits and all
extra blood donations will be combined with regular care visits and regular
withdrawal of blood for diagnostic purposes.
Furthermore the participants will be asked to fill in questionnaires online.
The knowledge generated in this project will be useful to propose innovative
and personalized interventions to achieve better pregnancy outcomes in the
future in patients with systemic autoimmune diseases.