Immune Signatures Differ Between Healthy Vs Complicated Lupus Pregnancies

By Reuters Staff

April 17, 2019

NEW YORK (Reuters Health) - Healthy and uncomplicated lupus pregnancies have similar immune signatures that differ from those in complicated lupus pregnancies, researchers report.

Women with systemic lupus erythematosus (SLE) face an increased risk of pregnancy complications, including preeclampsia, fetal or neonatal death and fetal morbidity. Identifying women likely to experience such complications remains challenging.

Dr. Virginia Pascual from Weill Cornell Medicine, in New York City, and colleagues evaluated the blood transcriptomes of 92 women with SLE and 43 healthy women during pregnancy and postpartum and 25 healthy women undergoing assisted reproductive technology (ART).

Healthy pregnant women and women with SLE who experienced uncomplicated pregnancies showed similar gene expression patterns, including down-regulation of interferon, lymphoid and plasma-cell modules and up-regulation of neutrophil and erythropoiesis modules.

In contrast, women with SLE who developed preeclampsia showed early regulation of neutrophil signatures that correlated with expansion of immature neutrophils, they team reports in the Journal of Experimental Medicine, online April 8.

Women with SLE whose pregnancies had fetal complications show the highest interferon and plasma cell signatures, as well as activated CD4+ T cell counts.

Transcriptional prediction signatures based on machine learning predicted SLE pregnancy-related preeclampsia with mean accuracy of 74.2%, compared with 67.8% based on laboratory/clinical parameters. Prediction of other complications using a similar machine-learning approach yielded low accuracy.

"These results suggest that both innate and adaptive arms of immunity are modulated at early stages of SLE pregnancy and that their dysregulation associates with the development of complications," the researchers conclude. "Overall, and although further validation in independent cohorts is warranted, our data suggest that early transcriptional changes in maternal blood might help predict preeclampsia in the context of SLE."

They add, "Our findings provide a framework for future studies aimed at investigating these immunological pathways and developing therapeutic strategies to improve health outcomes for mothers with SLE and their offspring."

Dr. Pascual did not respond to a request for comments.


J Exp Med 2019.