Increased circulating miR-155 identifies a subtype of preeclamptic patients.

INTRODUCTION: Preeclampsia is a common and severe pregnancy complication. The syndrome is highly heterogeneous, making accurate classification difficult, which is not conductive to find ways to predict and prevent this syndrome. Recently, we reported that high placental miR-155 defined a new subtype of preeclampsia. Here, we aimed to examine whether high maternal sero-miR-155 could be a marker to identify this subtype. METHODS: To explore whether the patients with high sero-miR-155 no matter in first and third trimester, we conducted a case-control and a longitudinal cohort study. We measured the sero-miR-155 levels at first, second and third trimesters in all pregnant women. Then, using the 95th percentile (P95) of sero-miR-155 in controls as the cut-off value, we divided the preeclamptic patients into high sero-miR-155 group (≥ P95) and normal sero-miR-155 group (< P95). We compared the difference of clinical manifestations between two groups and used t-distributed stochastic neighbor embedding (t-SNE) to evaluate whether the patients with high sero-miR-155 could be clustered as a subtype. Finally, we evaluated the predictive value of sero-miR-155 in the subtype. RESULTS: The case-control study included 525 subjects (350 controls and 175 preeclampsia) and the longitudinal cohort study included 411 subjects (274 controls and 137 preeclampsia). Sero-miR-155 was significantly elevated in preeclampsia. Compared with preeclamptic patients with normal sero-miR-155 levels, the cases with high sero-miR-155 had significantly higher blood pressure and other severe preeclampsia-related complications. The incidences of HELLP syndrome [5.2% (5/96) vs. 0.9% (2/216), p < 0.01], visual disturbance [15.6% (15/96) vs. 4.6% (10/216), p < 0.01], hypertensive retinopathy [13.5% (13/96) vs. 3.2% (7/216), p < 0.01], and placenta abruption [7.3% (7/96) vs. 0.9% (2/216), p < 0.01] in patients with high miR-155 level were significantly increased. T-SNE analysis showed the patients with high sero-miR-155 were predominantly clustered on the left of the plot. CONCLUSIONS: The patients with high sero-miR-155 exhibited more severe clinical manifestations and sero-miR-155 could be a biomarker to identify a subtype of preeclampsia with high sero-miR-155.