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Nucleic acids and polypeptides useful for diagnosing and treating complications of pregnancy

A technology of polypeptides and nucleic acid molecules, which is applied in the fields of diagnosis, disease diagnosis, diagnostic recording/measurement, etc., and can solve problems such as the unidentified role of proteins

Inactive Publication Date: 2008-11-05
BETH ISRAEL DEACONESS MEDICAL CENT INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although several of these factors have been identified, such as VEGF and PlGF, there are still many proteins whose roles in the pathogenesis of preeclampsia or seizures have not yet been identified

Method used

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  • Nucleic acids and polypeptides useful for diagnosing and treating complications of pregnancy
  • Nucleic acids and polypeptides useful for diagnosing and treating complications of pregnancy
  • Nucleic acids and polypeptides useful for diagnosing and treating complications of pregnancy

Examples

Experimental program
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preparation example Construction

[0235] Antibody preparation

[0236]Monoclonal antibodies that specifically bind any polypeptide of the invention can be produced by methods known in the art. These methods include Kohler and Milstein (Nature, 256:495-497, 1975) and Campbell ("Monoclonal Antibody Technology, The Production and Characterization of Rodent and Human hybrid omas", Burdon et al., Eds., Laboratory technique in Biochemistry and Molecular Biology, Volume 13, Elsevier Science Publishers, Amsterdam, 1985), and the recombinant DNA method described by Huse et al. (Science, 246, 1275-1281, 1989).

[0237] Monoclonal antibodies can be used in the supernatant of cultured hybridoma cells or ascites fluid induced by intraperitoneal inoculation of hybridoma cells into mice. The hybridoma technique, originally described by Kohler and Milstein (Eur. J. Immunol, 6, 511-519, 1976), has been widely used to generate hybrid cell lines that secrete high levels of monoclonal antibodies directed against any specific ant...

Embodiment 1

[0284] Example 1. Gene expression patterns in placental tissue from preeclamptic and normotensive women

[0285] To identify novel secreted factors involved in the pathogenesis of preeclampsia, we analyzed gene expression patterns in placental tissues from 19 women with preeclampsia and 15 normotensive women using Affymetrix U95A microarrays (see Table 1 ).

[0286] Table 1: Clinical characteristics of study patients

[0287] Normal (n=15)

Preeclampsia (n=19)

Mother's age (years)

35.2

31.9

Pregnancy (weeks)

39.0

31.1 *

Primiparous (%)

19

81 *

Systolic BP(mm Hg)

107

167.2 **

Diastolic BP(mm Hg)

83

101.8 **

Proteinuria (g protein / g creat)

＜0.3

5.2 **

Serum uric acid (mg / dl)

NA

6.8

Hematocrit (%)

35.7

33.9

Platelet count (K / μl)

217

198

Serum creatinine (mg / dl)

0.5

0.6

...

Embodiment 2

[0303] Example 2. mRNA Expression of FIt-1 and sFlt-1 in Preeclampsia

[0304] Since the above clustering identified sFlt1 as well as other genes validated in the literature, we chose to utilize the sFlt1 validation array for its ability to identify predictive markers for pre-eclampsia. For these experiments, placental sFlt-1 mRNA expression from 3 patients with preeclampsia (P1, P2, P3) and 3 normotensive pregnant women (N1, N2, N3) was determined by Northern blot analysis ( Figure 4 ). The upper band (7.5 kb) is the full length Flt-1 mRNA, while the lower more abundant band (3.4 kb) is the alternatively spliced ​​sFlt-1 mRNA. Actin is included as a control and 28S is shown as an arrow. These results show increased sFlt-1 gene expression for preeclampsia patients and confirm the set of predictive genes identified using the array as markers of preeclampsia or convulsions or a propensity to develop preeclampsia or convulsions.

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Abstract

Disclosed herein are methods for diagnosing or treating pregnancy related hypertensive disorders that include the use of a polypeptide or a nucleic acid encoding a polypeptide selected from the following: follistatin related protein, interleukin 8, inhibin A, VEGF-C, angiogenin, beta fertilin, hypothetical protein, leukocyte associated Ig-like receptor secreted protein, erythroid differentiation protein, adipogenesis inhibitory factor, corticotropin releasing factor binding protein, alpha-1- anti-chymotrypsin, insulin-like growth factor binding protein-5, CD33L, cytokine receptor like factor 1, platelet derived endothelial growth factor, lysyl hydroxylase isoform 2, stanniocalcin precursor, secreted frizzled related protein, galectin-3, alpha defensin, ADAM-TS3, cholecystokinin precursor, interferon stimulated T-cell alpha chemoattractant precursor, azurocidin, sperminine oxidase, UDP glycosyltransferase 2 family polypeptide B28, neurotrophic tyrosine kinase receptor 2, neutral endopeptidase, CDC28 protein kinase regulatory subunit 2, beta glucosidase, lanosterol synthase, calcium / calmodulin-dependent serine protein kinase, estrogen receptor-alternatively spliced transcript H, chemokine (CX3C motif) receptor 1, tyrosinase-related protein 1, hydoxy-delta-5-steroid dehyrogenase, dihydropyramidinase-like-4, and cytochrome P450-family 11.

Description

[0001] Statement Regarding Federally Funded Research [0002] This research was funded in part by NIH grant R03 DK064255-02. The US Government has certain rights in this invention. field of invention [0003] In a general sense, the present invention relates to the detection and treatment of individuals with pregnancy-related hypertensive disorders. Background of the invention [0004] Preeclampsia A syndrome of hypertension, edema, and proteinuria that affects 5-10% of pregnancies and results in substantial maternal and fetal morbidity and death. Preeclampsia is responsible for at least 200,000 maternal deaths per year worldwide. Symptoms of preeclampsia generally appear after the 20th week of pregnancy and are usually detected by a woman's blood pressure and urine routine tests. However, these diagnostic methods are not effective for the early diagnosis of the syndrome, which can reduce the risk to the individual or the developing fetus if effective treatment is availab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61B5/055C12Q1/68
CPCC12Q1/6883G01N33/6893G01N2800/321C12Q2600/158G01N2800/368C12Q2600/136G01N33/689C12Q1/00
Inventor S·A·卡鲁曼基V·P·苏克哈特姆
Owner BETH ISRAEL DEACONESS MEDICAL CENT INC
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