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Circulating Levels of sFlt1 Splice Variants as Predictive Markers for the Development of Preeclampsia.

Souders CA, Maynard SE, Yan J, Wang Y, Boatright NK, Sedan J, Balyozian D, Cheslock PS, Molrine DC, Simas TA - Int J Mol Sci (2015)

Bottom Line: Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14.These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format.It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

View Article: PubMed Central - PubMed

Affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA 02126, USA. Colby.Souders@UMassMed.edu.

ABSTRACT
Angiogenic biomarkers, including soluble fms-like tyrosine kinase 1 (sFlt1), are thought to be predictors of preeclampsia onset; however, improvement is needed before a widespread diagnostic test can be utilized. Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14. These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format. Data from this pilot study suggest that sFlt1-1 may be more predictive of preeclampsia than total sFlt1. It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

No MeSH data available.


Related in: MedlinePlus

sFlt1 isoform and VEGFR-1 quantitation from serum samples at three gestational windows (GW) during pregnancy. (A) sFlt1-1, (B) sFlt1-14 and (C) VEGFR-1 levels from all women included in the study and (D–F, respectively) a subset from women included in A–C diagnosed with chronic hypertension and/or diabetes mellitus (chtn_dm) are reported as the mean biomarker level ± SEM. *p ≤ 0.05; **p ≤ 0.01.
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ijms-16-12436-f005: sFlt1 isoform and VEGFR-1 quantitation from serum samples at three gestational windows (GW) during pregnancy. (A) sFlt1-1, (B) sFlt1-14 and (C) VEGFR-1 levels from all women included in the study and (D–F, respectively) a subset from women included in A–C diagnosed with chronic hypertension and/or diabetes mellitus (chtn_dm) are reported as the mean biomarker level ± SEM. *p ≤ 0.05; **p ≤ 0.01.

Mentions: Longitudinal serum samples prospectively collected under IRB approval from pregnant women [31,32] included women with or without risk factors for preeclampsia. Complete cohort demographics are illustrated in Table 1. Samples were analyzed for their concentration of sFlt1 splice variants using a capture ELISA format with mAbs Ex14-1 and 1CKLH18 to detect sFlt1-14 and sFlt1-1 splice variants, respectively. These results were compared to the concentration of total sFlt1 levels (VEGFR-1) that had been measured previously for each sample using a Quantikine ELISA Kit. The concentrations of serum sFlt1-1, sFlt1-14 and total sFlt1 (VEGFR-1) were compared between women with a singleton gestation who developed preeclampsia (PE) to those women who did not develop preeclampsia (Control) (Figure 5A–C) for three gestational age windows (GW): 21–27.99 weeks (GW1); 28–31.99 weeks (GW2): and >32 weeks (GW3). Concentrations of the sFlt1-1 variant were significantly higher in women with preeclampsia (n = 13) compared to controls (n = 124) for the earliest gestational window (GW1). In addition, sFlt1-1 and sFlt1-14 measurements were both significantly higher in women with preeclampsia (n = 12) compared to controls (n = 115) in GW2. VEGFR-1 measurements were not significantly different between women with preeclampsia as compared to controls for GW1 or GW2; however, VEGFR-1, sFlt1-1 and sFlt1-14 concentrations were significantly different between women with preeclampsia (n = 10) compared to control women (n = 121) for GW3.


Circulating Levels of sFlt1 Splice Variants as Predictive Markers for the Development of Preeclampsia.

Souders CA, Maynard SE, Yan J, Wang Y, Boatright NK, Sedan J, Balyozian D, Cheslock PS, Molrine DC, Simas TA - Int J Mol Sci (2015)

sFlt1 isoform and VEGFR-1 quantitation from serum samples at three gestational windows (GW) during pregnancy. (A) sFlt1-1, (B) sFlt1-14 and (C) VEGFR-1 levels from all women included in the study and (D–F, respectively) a subset from women included in A–C diagnosed with chronic hypertension and/or diabetes mellitus (chtn_dm) are reported as the mean biomarker level ± SEM. *p ≤ 0.05; **p ≤ 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490453&req=5

ijms-16-12436-f005: sFlt1 isoform and VEGFR-1 quantitation from serum samples at three gestational windows (GW) during pregnancy. (A) sFlt1-1, (B) sFlt1-14 and (C) VEGFR-1 levels from all women included in the study and (D–F, respectively) a subset from women included in A–C diagnosed with chronic hypertension and/or diabetes mellitus (chtn_dm) are reported as the mean biomarker level ± SEM. *p ≤ 0.05; **p ≤ 0.01.
Mentions: Longitudinal serum samples prospectively collected under IRB approval from pregnant women [31,32] included women with or without risk factors for preeclampsia. Complete cohort demographics are illustrated in Table 1. Samples were analyzed for their concentration of sFlt1 splice variants using a capture ELISA format with mAbs Ex14-1 and 1CKLH18 to detect sFlt1-14 and sFlt1-1 splice variants, respectively. These results were compared to the concentration of total sFlt1 levels (VEGFR-1) that had been measured previously for each sample using a Quantikine ELISA Kit. The concentrations of serum sFlt1-1, sFlt1-14 and total sFlt1 (VEGFR-1) were compared between women with a singleton gestation who developed preeclampsia (PE) to those women who did not develop preeclampsia (Control) (Figure 5A–C) for three gestational age windows (GW): 21–27.99 weeks (GW1); 28–31.99 weeks (GW2): and >32 weeks (GW3). Concentrations of the sFlt1-1 variant were significantly higher in women with preeclampsia (n = 13) compared to controls (n = 124) for the earliest gestational window (GW1). In addition, sFlt1-1 and sFlt1-14 measurements were both significantly higher in women with preeclampsia (n = 12) compared to controls (n = 115) in GW2. VEGFR-1 measurements were not significantly different between women with preeclampsia as compared to controls for GW1 or GW2; however, VEGFR-1, sFlt1-1 and sFlt1-14 concentrations were significantly different between women with preeclampsia (n = 10) compared to control women (n = 121) for GW3.

Bottom Line: Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14.These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format.It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

View Article: PubMed Central - PubMed

Affiliation: MassBiologics of the University of Massachusetts Medical School, Boston, MA 02126, USA. Colby.Souders@UMassMed.edu.

ABSTRACT
Angiogenic biomarkers, including soluble fms-like tyrosine kinase 1 (sFlt1), are thought to be predictors of preeclampsia onset; however, improvement is needed before a widespread diagnostic test can be utilized. Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14. These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format. Data from this pilot study suggest that sFlt1-1 may be more predictive of preeclampsia than total sFlt1. It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

No MeSH data available.


Related in: MedlinePlus