Rowson S, Reddy M, De Guingand D L, Langston-Cox A, Marshall S A, da Silva Costa F, Palmer K R
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia; Monash Health, Department of Obstetrics and Gynaecology, Clayton, Victoria, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Placenta. 2022 Mar 24;120:73-78. doi: 10.1016/j.placenta.2022.02.017. Epub 2022 Feb 24.
Soluble fms-like tyrosine kinase 1 (sFLT-1), a circulating anti-angiogenic factor that binds and antagonizes placental growth factor (PlGF), appears key to preeclamptic pathophysiology. Two main sFLT-1 splice variants exist: sFLT-1 e15a and sFLT-1 i13. Total sFLT-1/PlGF ratios are increasingly used clinically; we explore whether using placental-specific sFLT-1 e15a improves test performance compared with total sFLT-1 in preeclampsia diagnosis.
Consent was obtained for serum sampling from 96 women with suspected preeclampsia. Total sFLT-1 and PlGF were quantified using the B.R.A.H.M.S Kryptor Compact Plus automated immunoassay platform, and sFLT-1 e15a by custom enzyme-linked immunosorbent assay. Test performance was then assessed by subsequent diagnosis.
Of 96 participants, 32 did not develop preeclampsia, 32 had early-onset (<34 weeks') disease and 32 had late-onset (≥34 weeks') disease. In those with preeclampsia, median sFLT-1 and sFLT-1 e15a were significantly increased (7361.0 vs 2463.0 pg/mL, and 946.6 vs 305.4 ng/mL respectively; p < 0.001 for both), and PlGF significantly reduced (43.5 vs 154.4 pg/mL; p < 0.001) compared to those without preeclampsia. Those with early-onset, compared to late-onset, preeclampsia chiefly had lower median PlGF levels (16.0 vs 57.3; p < 0.001), which contributed to higher sFLT-1/PlGF and sFLT-1 e15a/PlGF ratios (830.1 vs 86.7, and 109258.9 vs 12608.7 respectively; p < 0.001 for both).
sFLT-1 e15a performs comparably to total sFLT-1 in women with suspected preeclampsia, however with higher translational burden. Our results support the expanding clinical use of the sFLT-1/PlGF ratio in suspected preeclampsia, particularly early-onset, to assist with disease diagnosis.
可溶性fms样酪氨酸激酶1（sFLT-1）是一种循环抗血管生成因子，可结合并拮抗胎盘生长因子（PlGF），似乎是子痫前期病理生理学的关键因素。存在两种主要的sFLT-1剪接变体：sFLT-1 e15a和sFLT-1 i13。总sFLT-1/PlGF比值在临床上的应用越来越广泛；我们探讨在子痫前期诊断中，与总sFLT-1相比，使用胎盘特异性sFLT-1 e15a是否能提高检测性能。
获得了96例疑似子痫前期妇女的血清采样同意。使用B.R.A.H.M.S Kryptor Compact Plus自动免疫分析平台对总sFLT-1和PlGF进行定量，并通过定制酶联免疫吸附测定法对sFLT-1 e15a进行定量。然后通过后续诊断评估检测性能。
96名参与者中，32人未发生子痫前期，32人患有早发型（<34周）疾病，32人患有晚发型（≥34周）疾病。与未患子痫前期的人相比，子痫前期患者的sFLT-1和sFLT-1 e15a中位数显著升高（分别为7361.0 vs 2463.0 pg/mL和946.6 vs 305.4 ng/mL；两者p均<0.001），而PlGF显著降低（43.5 vs 154.4 pg/mL；p<0.001）。早发型子痫前期患者与晚发型子痫前期患者相比，主要是PlGF中位数水平较低（16.0 vs 57.3；p<0.001），这导致sFLT-1/PlGF和sFLT-1 e15a/PlGF比值更高（分别为830.1 vs 86.7和109258.9 vs 12608.7；两者p均<0.001）。
在疑似子痫前期的妇女中，sFLT-1 e15a的表现与总sFLT-1相当，然而其转化负担更高。我们的结果支持在疑似子痫前期，特别是早发型子痫前期中扩大sFLT-1/PlGF比值的临床应用，以辅助疾病诊断。
