Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis

Kalousová, Marta; Dusilová-Sulková, Sylvie; Kubêna, Aleŝ; Zakiyanov, Oskar; Levová, Kateřina; Bocková, Markéta; Gedeonova, Erika; Song, Xue; Ermini, Maria Laura; Špringer, Tomáš; Homola, Jiřı́; Tesař, Vladimı́r; Zima, Tomáš

doi:10.1159/000479847

Cited by 3 publications

(4 citation statements)

References 41 publications

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“…They also measured PAPP-A2 with an SPR biosensor in long-term hemodialysis patients, and found that PAPP-A2 was increased in these patients. 4 In our previous study, we further demonstrated that a functionalized GO-based SPR biosensor had higher sensitivity, affinity and selective ability for PAPP-A2 than a traditional SPR biosensor. In this pilot study, we first used a GO-based SPR biosensor to simultaneously measure PAPP-A and PAPP-A2.…”

Section: Mixed Sample Investigation and Interference Test With The Gomentioning

confidence: 86%

“…Previous studies using traditional SPR biosensors to measure various types of antigen-antibody reactions of PAPP-A and PAPP-A2 have shown promising results (Table 1). 4,[25][26][27][28][29][30] Mikkelsen et al 25 used SPR biosensors to assess the binding of pituitary adenylate cyclase-activating polypeptide type 1 (PAC1) receptor, a monoclonal single-chain fragment variable (scFv) antibody, to immobilize PAPP-A in the presence of calcium ions. They also investigated interactions between PAPP-A and recombinant antibodies PAC1-D8-scFv or PAC1-D8-mIgG2a in multiple animal species using SPR biosensors.…”

Section: Mixed Sample Investigation and Interference Test With The Gomentioning

confidence: 99%

“…23,24 Previous studies have used SPR biosensors to measure PAPP-A [25][26][27][28] and PAPP-A2. 4,29,30 In our previous study, we demonstrated that a functionalized GO-based SPR biosensor had higher sensitivity, affinity and selective ability for PAPP-A2 than a traditional SPR biosensor. 30 However, no previous study has simultaneously measured both PAPP-A and PAPP-A2 using a GO-based SPR biosensor.…”

Section: Introductionmentioning

confidence: 98%

“…Similar to PAPP-A, PAPP-A2 originates primarily from the placenta, but its expression is not limited to pregnancy. 4 Both PAPP-A and PAPP-A2 participate in fetal growth and development by cleaving IGFBPs, which can increase IGF bioavailability and bioactivity. 5 PAPP-A and PAPP-A2 are secreted into the maternal circulation and have been shown to be valuable biomarkers for pregnancyassociated diseases.…”

Section: Introductionmentioning

confidence: 99%

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<p>Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-a and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor</p>

Fan¹,

Chiu²,

Chen³

et al. 2020

IJN

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Background: Pregnancy-associated plasma protein-A and-A2 (PAPP-A and-A2) are principally expressed in placental trophoblasts and play a critical role in the regulation of fetal and placental growth. PAPP-A2 shares 45% amino acid similarity with PAPP-A. This study aimed to investigate the efficacy of real-time detection of PAPP-A and PAPP-A2 using a novel surface plasmon resonance (SPR) biosensor based on graphene oxide (GO). Methods: Traditional SPR and GO-based SPR chips were fabricated to measure PAPP-A and PAPP-A2 concentrations. We compared SPR response curves of PAPP-A and PAPP-A2 between traditional SPR and GO-SPR biosensors. We also performed interference tests and specificity analyses among PAPP-A, PAPP-A2, and mixed interference proteins. Results: The time to detect PAPP-A and PAPP-A2 was about 150 seconds with both traditional SPR and GO-SPR biosensors. Approximately double SPR angle shifts were noted with the GO-SPR biosensor compared to the traditional SPR biosensor at a PAPP-A and PAPP-A2 concentration of 5 μg/mL. The limit of detection of the GO-SPR biosensor was as low as 0.5 ng/mL for both PAPP-A and PAPP-A2. Interference testing revealed that almost all of the protein bonded on the GO-SPR biosensor with anti-PAPP-A from the mixture of proteins was PAPP-A, and that almost no other proteins were captured except for PAPP-A2. However, the SPR signal of PAPP-A2 (5.75 mdeg) was much smaller than that of PAPP-A (13.76 mdeg). Similar results were noted with anti-PAPP-A2, where almost all of the protein bonded on the GO-SPR biosensor was PAPP-A2. The SPR signal of PAPP-A (5.17 mdeg) was much smaller than that of PAPP-A2 (13.94 mdeg). Conclusion: The GO-SPR biosensor could distinguish PAPP-A and PAPP-A2 from various mixed interference proteins with high sensitivity and specificity. It could potentially be used to measure PAPP-A and PAPP-A2 in clinical blood samples during pregnancy.

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Section: Mixed Sample Investigation and Interference Test With The Gomentioning

confidence: 86%

Section: Mixed Sample Investigation and Interference Test With The Gomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

<p>Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-a and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor</p>

Fan¹,

Chiu²,

Chen³

et al. 2020

IJN

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Immunoassay-Amplified Responses Using a Functionalized MoS2-Based SPR Biosensor to Detect PAPP-A2 in Maternal Serum Samples to Screen for Fetal Down’s Syndrome

Chiu¹,

Tai²,

Nurrohman

et al. 2021

IJN

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Background Due to educational, social and economic reasons, more and more women are delaying childbirth. However, advanced maternal age is associated with several adverse pregnancy outcomes, and in particular a high risk of Down’s syndrome (DS). Hence, it is increasingly important to be able to detect fetal Down’s syndrome (FDS). Methods We developed an effective, highly sensitive, surface plasmon resonance (SPR) biosensor with biochemically amplified responses using carboxyl-molybdenum disulfide (MoS 2 ) film. The use of carboxylic acid as a surface modifier of MoS 2 promoted dispersion and formed specific three-dimensional coordination sites. The carboxylic acid immobilized unmodified antibodies in a way that enhanced the bioaffinity of MoS 2 and preserved biorecognition properties of the SPR sensor surface. Complete antigen pregnancy-associated plasma protein-A2 (PAPP-A2) conjugated with the carboxyl-MoS 2 -modified gold chip to amplify the signal and improve detection sensitivity. This heterostructure interface had a high work function, and thus improved the efficiency of the electric field energy of the surface plasmon. These results provide evidence that the interface electric field improved performance of the SPR biosensor. Results The carboxyl-MoS 2 -based SPR biosensor was used successfully to evaluate PAPP-A2 level for fetal Down’s syndrome screening in maternal serum samples. The detection limit was 0.05 pg/mL, and the linear working range was 0.1 to 1100 pg/mL. The women with an SPR angle >46.57 m° were more closely associated with fetal Down’s syndrome. Once optimized for serum Down’s syndrome screening, an average recovery of 95.2% and relative standard deviation of 8.5% were obtained. Our findings suggest that carboxyl-MoS 2 -based SPR technology may have advantages over conventional ELISA in certain situations. Conclusion Carboxyl-MoS 2 -based SPR biosensors can be used as a new diagnostic technology to respond to the increasing need for fetal Down’s syndrome screening in maternal serum samples. Our results demonstrated that the carboxyl-MoS 2 -based SPR biosensor was capable of determining PAPP-A2 levels with acceptable accuracy and recovery. We hope that this technology will be investigated in diverse clinical trials and in real case applications for screening and early diagnosis in the future.

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Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: A prospective observational cohort study

Kalousová

Dusilová-Sulková²,

Kubêna³

et al. 2019

Physiol Res

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Sclerostin is a protein which is involved in bone metabolism and probably also in vessel wall function. This prospective observational cohort study evaluated the prognostic significance of sclerostin in hemodialysis (HD) patients. In total, 106 HD patients and 25 healthy controls participated in the study. HD patients were prospectively followed up for five years. Sclerostin was measured in serum using standard ELISA kits by Biomedica. Sclerostin concentrations in serum were higher in HD patients compared to the controls (89.2±40.3 pmol/l vs. 32.8±13.0 pmol/l, p<0.001). Sclerostin levels were significant for cardiovascular mortality but not for overall mortality and mortality due to infection. A higher cardiovascular risk was connected to sclerostin concentrations above the median (>84 pmol/l), HR (95 % CI): 2.577 (1.0002-10.207), p=0.04. When sclerostin was evaluated together with residual diuresis in Kaplan-Meier analysis the worst prognosis due to cardiovascular events was observed in the group with high sclerostin and zero residual diuresis compared to all other patients (p=0.007). In summary, serum sclerostin levels in HD patients were increased when compared to healthy subjects. High sclerostin levels were demonstrated as a risk factor for cardiovascular mortality. Further studies are required to clarify the pathophysiological mechanisms of sclerostin action in patients with renal failure before therapeutic measures can be established.

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Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis

Cited by 3 publications

References 41 publications

<p>Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-a and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor</p>

<p>Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-a and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor</p>

Immunoassay-Amplified Responses Using a Functionalized MoS2-Based SPR Biosensor to Detect PAPP-A2 in Maternal Serum Samples to Screen for Fetal Down’s Syndrome

Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: A prospective observational cohort study

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