Soluble Fms-like Tyrosine Kinase 1 (sFlt-1): A Precise Predictor of Pregnancy-Related Risks

Soluble Fms-like Tyrosine Kinase 1 (sFlt-1): A Precise Predictor of Pregnancy-Related Risks
Preeclampsia is an acute and severe disorder that can lead to preterm birth in up to 15% of affected pregnancies. It is estimated that approximately 3% to 7% of pregnancies globally are complicated by preeclampsia. Preeclampsia occurs after the 20th week of gestation, characterized by the onset of new hypertension or worsening of pre-existing hypertension, along with proteinuria. In severe cases, preeclampsia can progress to eclampsia, which is characterized by generalized convulsions and can lead to maternal organ damage, placental abruption, or fetal preterm birth. Eclampsia is responsible for 42% of maternal deaths. Once preeclampsia occurs, it can only be alleviated after delivery. Therefore, preventive treatment is a crucial focus in the management of preeclampsia.
Soluble fms-like tyrosine kinase-1 (sFlt-1), also known as soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), is a glycoprotein with tyrosine kinase activity and belongs to the soluble splice variant subtype of VEGFR-1. sFlt-1 contains only the extracellular ligand-binding domain, lacking the cytoplasmic domain and transmembrane helix structure. The Flt-1 gene encodes mRNA with 30 exons, and its precursor mRNA is spliced into multiple soluble splice variants, including sFlt-1-1-i13, sFlt-1-1-i14, sFlt-1-1-i15a, and sFlt-1-1-i15b, all of which are associated with the antagonism of placental growth factor (PlGF) [1].

Figure 1: Structural and Functional Differences Between Flt-1 and sFlt-1

 

sFlt-1 is primarily produced by the placenta. Abnormal production of sFlt-1 by trophoblasts and its subsequent release into the circulation can competitively bind to PlGF and VEGF-A, antagonizing the biological activity and signaling of VEGF and PlGF, thereby inhibiting placental angiogenesis. This leads to impaired placental vascular remodeling, which in turn promotes the secretion of more sFlt-1 by the placenta, resulting in endothelial dysfunction and systemic maternal disease, and inducing the occurrence and progression of preeclampsia [2].

Figure 2: Impact of Preeclampsia

 

Clinically, sFlt-1 has been widely used for the diagnosis and prognosis of preeclampsia, reflecting the growth of placental vessels and fetal growth restriction. Studies have reported that in patients with preeclampsia, sFlt-1 levels are elevated at the mRNA level, and ELISA detection shows that serum sFlt-1 concentrations in patients are five times higher than in normally pregnant women. Moreover, as gestational age increases, the levels of sFlt-1 initially decrease slightly and then increase. Detection of sFlt-1 levels in maternal serum is of significant importance [3].
The serum protein ratio of sFlt-1/PlGF has been recognized as a predictive biomarker for preeclampsia and fetal growth restriction (FGR). At a false-positive rate of 10%, the sFlt-1/PlGF ratio can predict 53% of early-onset preeclampsia [4].

Figure 3: Clinical Value of the sFlt-1/PlGF Ratio in Diagnosis

 

The "Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy 2020" indicate that the sFlt-1/PlGF ratio can be used for short-term prediction of preeclampsia and FGR prediction. A single cutoff value of 38 is of significant value for excluding preeclampsia within one week [5][6]:
  • sFlt-1/PlGF ratio ≤ 38: Negative predictive value (excluding preeclampsia within one week) is 99.3%.
  • sFlt-1/PlGF ratio > 38: Positive predictive value (predicting preeclampsia within four weeks) is 36.7%.
The sFlt-1/PlGF ratio also has significant clinical value in the auxiliary diagnosis of preeclampsia and assessment of disease severity, with a positive correlation with disease severity [7]:
  • sFlt-1/PlGF ratio < 33: Excludes preeclampsia.
  • sFlt-1/PlGF ratio > 85: Early-onset (20–33+6 weeks), diagnosis of preeclampsia.
  • sFlt-1/PlGF ratio > 110: Late-onset (34 weeks to delivery), diagnosis of preeclampsia.
As a diagnostic biomarker for eclampsia, sFlt-1/PlGF can facilitate early diagnosis and prevention, reflecting the growth of placental vessels and fetal growth restriction. It is a key indicator for predicting the risk of preeclampsia and FGR, effectively reducing pregnancy-related risks and mortality.

S-RMab® Monoclonal Antibody Pair

Starter has  introduced a highly sensitive sFlt-1 mouse monoclonal antibody and now offers multiple pairs of high-specificity sFlt-1 rabbit/mouse antibodies. The sensitivity for detecting and quality controlling the target protein is less than 10 pg/ml!

We are dedicated to providing high-quality raw materials for sFlt-1 detection to our global partners and offering more accurate and reliable diagnostic services to patients worldwide. Inquiries are welcome.

 

Product Information

 

Gatalog Num Product Name Product Parameters Price
S0B3144 IGFBP4 Recombinant Rabbit mAb (SDT-187-35) Host : Rabbit Inquiry
Conjugation : Unconjugated
S0B3143 IGFBP4 Recombinant Mouse mAb (SDT-185-H182) Host : Mouse Inquiry
Conjugation : Unconjugated
S0B3142 sFlt-1 Recombinant Rabbit mAb (SDT-233-2) Host : Rabbit $645 
Conjugation : Unconjugated
S0B3141 sFlt-1 Recombinant Rabbit mAb (SDT-233-26-2) Host : Rabbit $645 
Conjugation : Unconjugated
S0B3140 sFlt-1 Recombinant Rabbit mAb (SDT-233-26) Host : Rabbit $645 
Conjugation : Unconjugated

 

Reference

[1] Palmer K R , Tong S , Kaitu'U-Lino T J .Placental-specific sFLT-1: role in pre-eclamptic pathophysiology and its translational possibilities for clinical prediction and diagnosis[J].Molecular Human Reproduction, 2016.

[2] Fan X, Rai A, Kambham N, Sung JF, Singh N, Petitt M, Dhal S, Agrawal R, Sutton RE, Druzin ML, Gambhir SS, Ambati BK, Cross JC, Nayak NR. Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications. J Clin Invest. 2014 Nov;124(11):4941-52.

[3]Maynard S E , Venkatesha S , Thadhani R ,et al.Soluble Fms-like Tyrosine Kinase 1 and Endothelial Dysfunction in the Pathogenesis of Preeclampsia[J].Pediatric Research, 2005, 57(5 Part 2):1R.

[4]Tianhua Hg, Shamim R, et al.Prenatal screening for preeclampsia: the roles of placental growth factor and pregnancy–associated plasma protein A in the first trimester and placental growth factor and soluble fms-like tyrosine kinase 1–placental growth factor ratio in the early second trimester[J].AJOG Global Reports,2023,3(2)

[5]The Chinese Society of Obstetrics and Gynecology, Pregnancy Hypertension Disease Group. Guidelines for Diagnosis and Treatment of Pregnancy Hypertension Diseases.(2020)[J].[2024-03-31].

[6]Leanos-Miranda, AlfredoGraciela Nolasco-Leanos, AnaIsmael Carrillo-Juarez, ReyesJose Molina-Perez, CarlosJanet Sillas-Pardo, LilianaManuel Jimenez-Trejo, LuisIsordia-Salas, IrmaLeticia Ramirez-Valenzuela, Karla.Usefulness of the sFlt-1/PlGF (Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor) Ratio in Diagnosis or Misdiagnosis in Women With Clinical Diagnosis of Preeclampsia[J].Hypertension: An Official Journal of the American Heart Association, 2020, 76(3).

[7]Verlohren S , Herraiz I , Lapaire O ,et al.New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia.[J].Hypertension, 2014, 63(2):346-352.