de Jesús Nilson R, de Jesús Guilherme R, Lacerda Marcela I, Dos Santos Flávia C, Nogueira Jeane de S, Porto Luiz Cristóvão, Coutinho Evandro S F, Klumb Evandro M
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Arthritis Care Res (Hoboken). 2025 Sep;77(9):1125-1134. doi: 10.1002/acr.25536. Epub 2025 May 2.
This study analyzed longitudinal trajectories of soluble Flt1 (sFlt1) levels, placenta growth factor (PlGF) levels, and sFlt1:PlGF ratios in a cohort of pregnant patients with systemic lupus erythematosus (SLE).
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 sFlt1, PlGF, and sFlt1:PlGF ratios. Patients were classified as inactive SLE (Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] <4), active disease (SLEPDAI ≥4), or preeclampsia (PE). Medians and interquartile ranges were calculated for each group, and linear models with random effects were used.
A total of 527 samples were obtained from 163 patients, and all patients were subsequently classified as having inactive disease (109 patients [66.9%]), active disease (33 patients [20.2%]), and inactive disease with PE (21 patients [12.9%]). In exploratory analysis, patients with PE had higher mean serum levels of sFlt1 and sFlt1: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 sFlt1 levels from the 24th week, constantly low PlGF levels from the 14th week, and progressive increase of sFlt1:PlGF ratio during pregnancy. All these differences were statistically significant compared to the groups without PE.
Pregnant patients with SLE who developed PE had higher sFlt1 levels and sFlt1: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.
本研究分析了一组患有系统性红斑狼疮(SLE)的孕妇中可溶性Flt1(sFlt1)水平、胎盘生长因子(PlGF)水平以及sFlt1:PlGF比值的纵向变化轨迹。
采集血样(孕14 - 18周、24 - 26周、30 - 32周、34 - 36周和38 - 40周),储存在 - 80°C ,并评估血清中sFlt1、PlGF水平以及sFlt1:PlGF比值。患者被分类为非活动性SLE(系统性红斑狼疮妊娠疾病活动指数[SLEPDAI]<4)、活动性疾病(SLEPDAI≥4)或先兆子痫(PE)。计算每组的中位数和四分位数间距,并使用具有随机效应的线性模型。
共从163例患者中获取了527份样本,所有患者随后被分类为患有非活动性疾病(109例患者[66.9%])、活动性疾病(33例患者[20.2%])以及伴有PE的非活动性疾病(21例患者[12.9%])。在探索性分析中,与非活动性和活动性SLE患者相比,PE患者的sFlt1平均血清水平和sFlt1:PlGF比值更高,而PlGF水平更低(P = 0.01至P < 0.001)。使用具有随机效应的线性模型,比较非活动性和活动性疾病时,这些血管生成标志物的平均血清水平无显著差异。PE患者在妊娠期间从第24周起sFlt1水平显著升高,从第14周起PlGF水平持续较低,且sFlt1:PlGF比值逐渐升高。与无PE的组相比,所有这些差异均具有统计学意义。
发生PE的SLE孕妇sFlt1水平和sFlt1:PlGF比值更高,PlGF水平更低,并且这后两个变化在孕中期开始时、临床表现出现之前就已被检测到。SLE活动并不干扰这些血管生成标志物的纵向变化情况。