Analysis of the longitudinal behavior of serum levels of Soluble Flt-1 and Placental Growth Factor in pregnant women with Systemic Lupus Erythematosus.

Abstract

Objective: This study analyzed longitudinal trajectories of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) and sFlt-1/PlGF ratio in a cohort of pregnant patients with systemic lupus erythematosus (SLE).

Methods: Blood samples were collected (14-18, 24-26, 30-32, 34-36 and 38-40 weeks), stored at -80°C and evaluated for serum levels of sFlt-1, PlGF and sFlt1/PlGF ratios. Patients were classified as inactive SLE (SLEPDAI < 4), active disease (SLEPDAI > 4), or preeclampsia (PE). Medians and interquartile ranges (IQR) were calculated for each group, and linear models with random effects were used.

Results: A total of 527 samples were obtained from 163 patients and all cases were subsequently classified as inactive disease [109 (66.9%)], active disease [33 (20.2%)], and inactive disease with PE [21 (12.9%)]. In exploratory analysis, patients with PE had higher mean serum levels of sFlt-1 and sFlt-1/PlGF ratios and lower PlGF levels than patients with inactive and active SLE (p=0.01 to p<0.001). Using linear models with random effects, there was no significant differences in mean serum levels of these angiogenic markers comparing inactive and active disease. Patients with PE showed a marked increase in sFlt-1 from the 24th week, constantly low PlGF levels from the 14th week and progressive increase of sFlt-1/ PlGF ratio during pregnancy. All these differences were statistically significant compared to the groups without PE.

Conclusion: Pregnant SLE patients who developed PE had higher sFlt-1 levels and sFlt-1/PlGF ratios, and lower PlGF levels, and these last two changes were detected at the beginning of second trimester, before clinical manifestation. SLE activity did not interfere with longitudinal behavior of these angiogenic markers.