Methods and devices for detecting biomarkers associated with preeclampsia

A biomarker and pre-eclampsia technology, applied in biochemical equipment and methods, measurement devices, microbial determination/testing, etc., can solve the problem of intensified identification of predictive biomarkers, comprehensive understanding of the pathogenesis of PE is out of reach, Difficulties in developing targeted therapy strategies

Pending Publication Date: 2020-09-04
IGENOMIX SL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Despite decades of research, a comprehensive understanding of PE pathogenesis remains elusive, exacerbating the difficulties involved in identifying predictive biomarkers and developing targeted therapeutic strategies

Method used

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  • Methods and devices for detecting biomarkers associated with preeclampsia
  • Methods and devices for detecting biomarkers associated with preeclampsia
  • Methods and devices for detecting biomarkers associated with preeclampsia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0314] Example 1: Human endometrial stromal cells from women with previous sPE pregnancies fail to decidualize in vitro

[0315] Decidualization of hESCs isolated from endometrial biopsy samples from patients with sPE in previous pregnancies (n=13) was assessed and compared to control patients with normal delivery outcomes (n=13). Table 2 summarizes the maternal and infant characteristics of the participants. hESCs were decidualized by treatment with cAMP and medroxyprogesterone acetate (MPA) for 5 days. As experimental controls, cells from the same donor were cultured in parallel in the absence of cAMP and MPA.

[0316] Localization of F-actin in decidual cells from non-abnormal pregnant women showed expected cytoskeletal remodeling and shape changes consistent with conversion of fibroblasts to the decidual phenotype ( Figure 1A ). In contrast, hESCs from women with sPE did not undergo these changes ( Figure 1B ). In non-decidualized hESCs, PRL detected in conditioned ...

Embodiment 2

[0318] Example 2: Alterations in the global transcriptional profile of decidualized hESCs from prior sPE patients.

[0319] To identify molecular changes in functional decidualization defects found in hESCs from women who had undergone sPE, a microarray strategy was used. Specifically, the transcriptomic analysis of non-decidualized and decidualized hESCs established from the normal pregnancy group and the sPE pregnancy group was performed in vitro ( Figure 2A ). Table 3 shows the clinical characteristics of the endometrial donors.

[0320] Figure 2B An overview of the results is given in . In the non-decidualized state, only 5 genes were differentially expressed between the control and sPE samples, and the fold difference was small ( Figure 2C ). Thus, at baseline, hESCs from patients with prior sPE were very similar to hESCs from control women.

[0321] The expression of 74 genes was significantly regulated ≥2-fold during decidualization in samples from control dono...

Embodiment 3

[0325] Example 3: In situ molecular defects in decidua basalis or parietal decidua from control versus sPE pregnancies

[0326] Isolate sections of the basal decidua (DB) or parietal decidua (DP) using laser microdissection. From gestational age-matched samples from women with sPE case versus control (from women with preterm birth (nPTB) without evidence of infection; Figure 3A ) to capture cells in tissue sections from biopsy samples. Table 8 summarizes the clinical characteristics of the participants.

[0327] Table 8. Maternal and Fetal Characteristics of Decidual Donors (Transcriptome Analysis of In Situ Expression of Decidual Genes in Severe Preeclampsia (sPE) vs. Spontaneous Preterm Birth Without Signs of Infection (NPTB))

[0328]

[0329] Mean ± SEM ** One-tailed Student's t-test

[0330] NA: not applicable

[0331] Figure 3B An overview of the results is shown in . In decidua basalis, 79 genes were significantly DE in sPE vs. nPTB, with smaller fold changes...

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Abstract

Provided herein, in some embodiments, are methods and compositions for detecting differentially expressed genes in a sample obtained from a subject having or at risk for preeclampsia.

Description

[0001] related application [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 554,471, filed September 5, 2017, the contents of which are incorporated herein by reference. technical field [0003] The methods and compositions described herein involve detecting differentially expressed genes (eg, biomarkers) that are indicative of having or being at risk of preeclampsia. Background technique [0004] Preeclampsia (PE) affects about 8% of first-time pregnancies and affects 8 million pairs of mothers and infants worldwide each year (Winn et al., Pregnancy Hypertens, 2011, 1(1): 100-108; Fisher, Am J Obstet Gynecol, 2015, 213(4Suppl):S115-122). This complication is unique to human pregnancy and is characterized by new onset hypertension, proteinuria, and other signs of maternal vascular damage such as edema (Roberts et al., Lancet, 2001, 357(9249):53-56 ). Diagnosis of severe preeclampsia (sPE) based on a further increase in blood pressure...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68C12Q1/6837
CPCC12Q1/6883G01N33/689C12Q2600/158C12Q1/6813C12Q1/686C12Q2561/113C12Q2565/626G01N33/54306G01N2333/4745G01N2333/5756G01N2333/90203G01N2800/368
Inventor 卡洛斯·西蒙苏珊·费希尔塔玛拉·加里多
Owner IGENOMIX SL
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