Complement factors and alpha‐fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects

Dong, Naixuan; Gu, Hui; Liú, Dan; Wei, Xiaowei; Ma, Wei; Ma, Lifang; Liu, Yusi; Yan, Wang; Jia, Shanshan; Huang, Jieting; Wang, Chenfei; He, Xuan; Huang, Tzung-Chi; He, Yiwen; Zhang, Qiang; An, Dong; Bai, Yuling; Yuan, Zhengwei

doi:10.1111/nyas.14443

Cited by 18 publications

(22 citation statements)

References 63 publications

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“…In metazoans, C3 interacts with many complement factors and non-complement proteins to play an essential role in immune regulation [ 22 ]. C3 protein is downregulated significantly in the serum of pregnant women with neural tube defects compared with the women carrying normal fetuses during pregnancy [ 23 ]. Plasma concentration of the C3 protein is increased gradually throughout pregnancy compared with nonpregnant women, suggesting that C3 plays a key role in normal placentation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…C1r expression is decreased in the implantation site of the preeclampsia model [ 18 ], and C2 deficiency results in thrombocytopenia during early pregnancy [ 19 ]. Neural tube defects in pregnant women lead to downregulation of the C3 protein in the serum compared with normal pregnant women [ 23 ]. Normal women have a lower level of C5b-9 in the villous trophoblast of the placentas [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

Yang

Wang

et al. 2021

Animals

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During early gestation in humans, complement regulation is essential for normal fetal growth. It is supposed that a complement pathway participates in maternal splenic immune regulation at the early stage of gestation in ewes. The aim of this study was to analyze the effects of early pregnancy on the expression of complement components in the maternal spleen of ewes. In this study, ovine spleens were sampled on day 16 of nonpregnancy, and days 13, 16 and 25 of gestation. RT-qPCR, Western blot and immunohistochemical analysis were used to detect the changes in expression of complement components in the ovine maternal spleens. Our results reveal that C1q was upregulated during early gestation, C1r, C1s, C2, C3 and C5b increased at day 25 of gestation and C4a and C9 peaked at days 13 and 16 of gestation. In addition, C3 protein was located in the capsule, trabeculae and splenic cords. In conclusion, our results show for the first time that there was modification in the expression of complement components in the ovine spleen at the early stage of gestation, and complement pathways may participate in modulating splenic immune responses at the early stage of gestation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

Yang

Wang

et al. 2021

Animals

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“…74 In a study from Yuan's laboratory, the serum from pregnant women carrying fetuses with NTD and women carrying normal fetuses was collected, and iTRAQ was used for differential proteomic analysis. 75 A total of 113 differentially expressed proteins were identified; complement factors C3 and C9 were significantly downregulated in the NTD group compared with those in the normal group. 75 Next, a machine learning method, support vector machine (SVM), was utilized to set up a disease prediction model for NTDs.…”

Section: Proteomicsmentioning

confidence: 99%

“…75 A total of 113 differentially expressed proteins were identified; complement factors C3 and C9 were significantly downregulated in the NTD group compared with those in the normal group. 75 Next, a machine learning method, support vector machine (SVM), was utilized to set up a disease prediction model for NTDs. As an increasingly prevalent method, machine learning can mine potential patterns in large datasets and then turn them into opportunities for early and accurate predictions.…”

Section: Proteomicsmentioning

confidence: 99%

Identifying biomarkers for prenatal diagnosis of neural tube defects based on “omics”

Huang

Yuan

2021

Clinical Genetics

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Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and societies. Presently, the clinical diagnosis of NTDs mainly relies on ultrasound images combined with certain indices, such as alpha-fetoprotein levels in the maternal serum and amniotic fluid. Recently, the discovery of additional biomarkers in maternal tissue has presented new possibilities for prenatal diagnosis. Over the past 20 years, "omics" techniques have provided the premise for the study of biomarkers. This review summarizes recent advances in candidate biomarkers for the prenatal diagnosis of fetal NTDs based on omics techniques using maternal biological specimens of different origins, including amniotic fluid, blood, and urine, which may provide a foundation for the early prenatal diagnosis of NTDs.

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“…[8,9] We previously combined the analysis of serum complements (including C1QA, C1S, and C3) and MSAFP to overcome the shortcomings of AFP analysis and improve the sensitivity and speci city of NTD screening. [10] Prenatal molecular biomarkers have the potential to help early screening, diagnosis and intervention. Therefore, nding more speci c and sensitive maternal serum biomarkers can help screening for NTDs in decentralized healthcare systems for the general population of pregnant women during early gestation.…”

Section: Introductionmentioning

confidence: 99%

CORO1A and DNM2 in Serum Exosomes as Biomarkers of Neural Tube Defects

Yan

Jia

et al. 2022

Preprint

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A highly specific and sensitive biomarker in maternal serology analysis for early diagnosis of neural tube defects (NTDs) is yet to be determined. Proteomics was utilized to identify novel specific proteins for NTDs and it revealed three differentially expressed proteins in fetal development. In a rat model with NTDs, we quantified proteins in maternal serum exosomes using western blotting on gestational days E18, E16, E14, and E12; in serum on E18 and E12; in neural tubes on E18 and E12; and in fetal neural exosomes on E18. Coronin 1A and Dynamin 2 expressions were exosome-specific and associated with spina bifida aperta embryogenesis and were proved to be downregulated in maternal serum exosomes from E12 to E18, in neural tubes and fetal neural exosomes with statistical difference, and in serum with no difference. Differentially expressed proteins were further analyzed in the serum exosomes of pregnant women during gestational weeks 12–40 using ELISA. Coronin 1A and Dynamin 2 were demonstrated to possess good diagnostic efficacy during gestation weeks 12–40, particularly during early gestation (12–18 weeks), and may be used as potential NTD screening and diagnostic biomarkers during early gestation.

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Complement factors and alpha‐fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects

Cited by 18 publications

References 63 publications

Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

Identifying biomarkers for prenatal diagnosis of neural tube defects based on “omics”

CORO1A and DNM2 in Serum Exosomes as Biomarkers of Neural Tube Defects

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