Preeclampsia is a heterogenous, multiorgan cardiovascular disorder of pregnancy. An early and reliable diagnostic test for preeclampsia would facilitate targeted surveillance and timely delivery, improving the odds of preventing major maternal complications and death. Here, we report the development of novel strip-based lateral flow assay (LFA) using Lanthanide-doped upconversion nanoparticles (UCNPs) conjugated to antibodies targeting two vascular biomarkers; FK506-binding protein like (FKBPL) and its target protein, cluster of differentiation 44 (CD44) [1]. We first used conventional ELISAs to measure circulating plasma FKBPL and CD44 protein concentrations from women with early-onset preeclampsia (EOPE, delivering <34 weeks) and gestational age-matched healthy controls. We confirmed that the CD44/FKBPL ratio is reduced in early-onset preeclampsia (EOPE 160±134, n = 38, vs control 245.2±106.7, n = 13, p = 0.0004) with a good diagnostic potential (AUC=0.81, p=0.0007). Using our rapid FKBPL and CD44-LFA prototypes, we achieved improved lower limit of detection: 10 pg/ml for FKBPL and 15 pg/ml for CD44. The FKBPL signal was significantly higher in early-onset preeclampsia (EOPE 2,685±459.2, n=42 vs control 2,142±324, n=15, p<0.0001), while the CD44 signal was significantly lower in early-onset preeclampsia (EOPE 2646±432, n=42 vs control 4235±1286, n=15, p<0.0001), compared to controls. Aligned with our ELISA results, this translated to a lower CD44/FKBPL ratio in early-onset preeclampsia compared to controls (EOPE 1.01±0.19, n=42 vs control 2.09±0.84, n=15, p<0.0001). Based on the ROC curve (AUC=0.98, p<0.0001), a cut-off point of 1.24 for CD44/FKBPL ratio (sensitivity of 90.48% and specificity of 100%) provided positive predictive value of 100% and the negative predictive value of 91%. This work demonstrates that our CD44/FKBPL LFA has the potential to be developed into a new low-cost, rapid and highly sensitive point-of-care test for preeclampsia.
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