The "Innate" Immune Signatures in Lupus Pregnancy

I attended the first plenary for this ACR and was pleased to hear more work stemming from the PROMISSE study (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus). This effort, the work of investigators including Drs. Salmon, Buyon, Kim, Lockshin and Laskin (to name a few), has aimed to translate findings from mouse models to human lupus patients with respect to pregnancy loss and/or intrauterine growth retardation associated with placental inflammation.

Seunghee Hong (#914) presented work on longitudinal blood transcriptomics to understand the immune network associated with lupus pregnancy complications. This case control study of PROMISSE patients included 135 pregnant patients (92 with SLE and 43 without), as well as 54 non-pregnant patients (34 healthy and 20 SLE patients). Blood was collected at four points during pregnancy and once post-partum, and the blood transcriptome was identified by microarray.

During healthy pregnancies, erythropoiesis and neutrophils were increased while the interferon and plasma cell signatures were decreased followed overall by a normalization of these signatures upon delivery. In non-complicated SLE pregnancies, things looked similar to healthy pregnancies overall but with less pronounced down-regulation of the plasma cell signature compared to healthy pregnant controls. Post-delivery, the plasma cell signature normalized while the interferon signature remained slightly reduced.

In lupus pregnancies complicated by pre-eclampsia or other complications (e.g. fetal, neonatal death, pre-term delivery, placental insufficiency or growth restriction), a lack of down-regulation of the interferon and plasma cell signature was observed. Moreover, in the pre-eclampsia SLE pregnancies, an early and persistent up-regulation of neutrophils was seen with expansion of immature neutrophils.

While complex to follow, this blood transcriptome study showed significant differences in immune signatures between healthy and lupus pregnancies as well as those with significant complications. The potential use of the neutrophil signature as a biomarker for pre-eclampsia is novel and will be followed by more work.

More reports from ACR 2016