Clinical Application of a Graphene Oxide-Based Surface Plasmon Resonance Biosensor to Measure First-Trimester Serum Pregnancy-Associated Plasma Protein-A/A2 Ratio to Predict Preeclampsia

基于氧化石墨烯的表面等离子体共振生物传感器的临床应用,用于测量妊娠早期血清妊娠相关血浆蛋白 A/A2 比率以预测先兆子痫

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作者:Chen-Yu Chen, Ying-Hao Wang, Chie-Pein Chen, Fang-Ju Sun, Yi-Yung Chen, Yu-Jun Huang, Nan-Fu Chiu

Background

Preeclampsia, a major cause of adverse pregnancy outcomes, involves metalloproteinases pregnancy-associated plasma protein (PAPP)-A and PAPP-A2 from placental trophoblasts. The graphene oxide (GO)-based surface plasmon resonance (SPR) biosensor has higher sensitivity, affinity, and selective ability than the traditional SPR biosensor. The

Conclusion

Measuring first-trimester serum PAPP-A/PAPP-A2 ratio using the GO-SPR biosensor could be a valuable method for early prediction of preeclampsia.

Methods

This prospective case-control study of pregnant women was conducted at MacKay Memorial Hospital, Taipei, Taiwan between January 2018 and June 2020. The SPR angle shifts of first-trimester serum PAPP-A, PAPP-A2, and PAPP-A/PAPP-A2 ratio measured using the GO-SPR biosensor were compared between preeclampsia and control groups.

Results

Serum samples from 185 pregnant women were collected, of whom 30 had preeclampsia (5 early-onset; 25 late-onset). The response time between the antibody-antigen association and dissociation only took about 200 seconds. The SPR angle shift of PAPP-A in the preeclampsia group was significantly smaller than that in the control group (median (interquartile range): 5.33 (4.55) versus 6.89 (4.10) millidegrees (mDeg), P = 0.008). Conversely, the SPR angle shift of PAPP-A2 in the preeclampsia group was significantly larger than that in the control group (5.70 (3.81) versus 3.63 (2.38) mDeg, P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict all preeclampsia of ≤ 0.76, with an area under the ROC curve (AUC) of 0.79 (95% CI 0.73-0.85, P < 0.001). Sub-group analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict early-onset preeclampsia of ≤ 0.53 (AUC 0.99, 95% CI 0.96-1.00, P < 0.001), and ≤ 0.73 to predict late-onset preeclampsia (AUC 0.75, 95% CI 0.68-0.81, P < 0.001).

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