Relevância das citocinas angiogênicas (VEGF e PlGF) e antiangiogênicas (sFlt-1) na assistência às pacientes grávidas com lúpus eritematoso sistêmico

Abstract

Systemic lupus erythematosus (SLE) disproportionately affects women compared to men, with greater incidence during the reproductive years. Despite a better understanding of the course of the disease and its treatment during pregnancy, high rates of compromised maternal and fetal well-being persist, especially in those who have active disease at conception or a previous history of lupus nephritis (LN). Disease activity during pregnancy can result in a higher incidence of fetal loss, preeclampsia (PE), premature birth, and small for gestational age newborns. PE and LN present similar clinical and laboratory manifestations, and the differential diagnosis between them is, even today, a challenge. The clinical and laboratory resources currently available in clinical practice for the diagnosis of LN may not be sufficient to make an accurate differential diagnosis in all cases. With the aim of studying the approach to this dilemma, two studies were designed, one cross-sectional (study 1) and the other longitudinal (study 2), which analyzed the behavior of angiogenic (VEGF and PlGF) and antiangiogenic (sFlt-1) cytokines in pregnant women with inactive SLE, active SLE and PE. The first study analyzed the serum levels of these cytokines in pregnant women with inactive SLE, those with active LN and those with SLE and PE. Patients with SLE and PE had an angiogenic and antiangiogenic profile similar to that of patients with PE without SLE—low PlGF and high sFlt-1, with an elevated sFlt-1/PlGF ratio. Serum VEGF levels were significantly higher in patients with active LN compared to patients in the other two groups. This study confirmed the potential use of these angiogenic and antiangiogenic factors as a differential diagnosis of PE and active LN. The second study analyzed the behavior of these cytokines throughout pregnancy. After delivery, patients were allocated into three groups—inactive SLE, active SLE and SLE with PE. The study demonstrated that SLE activity did not interfere with the behavior of these cytokine levels during pregnancy (active SLE was like inactive SLE) and that in patients who developed PE, sFlt-1 levels and the sFlt-1/PlGF ratio were higher, while PlGF levels were attenuated. These changes were significant at the beginning of the second trimester, even before the clinical manifestations of PE. The results reinforce the proposal to monitor serum levels of these cytokines in pregnant women with SLE to establish an early and accurate differential diagnosis between active disease and PE and to predict adverse events during pregnancy.