Abstract
The aim of the research presented in this thesis was to provide extended background knowledge concerning several biochemical markers, used for the medical evaluation of pregnant women with suspected or confirmed preeclampsia, in order to improve the reliability of monitoring. Plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are known to reflect renal filtration in non-pregnant settings, and the plasma proteins, C-reactive protein and serum amyloid A protein, are known to be sensitive markers of inflammation.
Despite pregnancy-related renal hyperfiltration, the plasma levels of beta-2 microglobulin, cystatin C and beta trace protein remained virtually unchanged in the first and second trimesters, with an elevation (20-40%) in the third trimester in a cross-sectional study including 398 women with uncomplicated pregnancies. In a case-control study including 57 women diagnosed with preeclampsia and 218 women with uncomplicated pregnancies, the protein levels were elevated further in women with preeclampsia, and the three plasma proteins had similar diagnostic capacities for the diagnosis of preeclampsia. The placental expression of cystatin C, a strong extracellular protease inhibitor, was up-regulated in the preeclamptic placenta at the mRNA and protein level in a study including placental tissue samples from 13 normal and 22 preeclamptic pregnancies. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization were used for the mRNA expression analysis and immuno-histochemistry and Western blotting were used for the protein expression analysis. In a cross-sectional study including 27 healthy women undergoing planned Caesarean section at term, the concentrations of beta-2 microglobulin, cystatin C and beta trace protein in the uterine vein and the antecubital vein were analysed. No significant concentration gradients were detected, indicating that utero-placental synthesis is not a major source of these proteins in the maternal circulation.
The acute-phase proteins, C-reactive protein and serum amyloid A protein were not increased in women with preeclampsia compared with women with normal pregnancy in a study of 299 healthy normotensive women with uncomplicated pregnancies and 57 women with preeclampsia. The acute-phase proteins therefore did not reflect the suggested inflammatory response to preeclampsia.
The plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are potential markers of preeclampsia and for the monitoring of renal deterioration as the condition progresses. The proteins could be useful in optimizing the monitoring and timing of delivery of women with preeclampsia.
Despite pregnancy-related renal hyperfiltration, the plasma levels of beta-2 microglobulin, cystatin C and beta trace protein remained virtually unchanged in the first and second trimesters, with an elevation (20-40%) in the third trimester in a cross-sectional study including 398 women with uncomplicated pregnancies. In a case-control study including 57 women diagnosed with preeclampsia and 218 women with uncomplicated pregnancies, the protein levels were elevated further in women with preeclampsia, and the three plasma proteins had similar diagnostic capacities for the diagnosis of preeclampsia. The placental expression of cystatin C, a strong extracellular protease inhibitor, was up-regulated in the preeclamptic placenta at the mRNA and protein level in a study including placental tissue samples from 13 normal and 22 preeclamptic pregnancies. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization were used for the mRNA expression analysis and immuno-histochemistry and Western blotting were used for the protein expression analysis. In a cross-sectional study including 27 healthy women undergoing planned Caesarean section at term, the concentrations of beta-2 microglobulin, cystatin C and beta trace protein in the uterine vein and the antecubital vein were analysed. No significant concentration gradients were detected, indicating that utero-placental synthesis is not a major source of these proteins in the maternal circulation.
The acute-phase proteins, C-reactive protein and serum amyloid A protein were not increased in women with preeclampsia compared with women with normal pregnancy in a study of 299 healthy normotensive women with uncomplicated pregnancies and 57 women with preeclampsia. The acute-phase proteins therefore did not reflect the suggested inflammatory response to preeclampsia.
The plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are potential markers of preeclampsia and for the monitoring of renal deterioration as the condition progresses. The proteins could be useful in optimizing the monitoring and timing of delivery of women with preeclampsia.
| Original language | English |
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| Qualification | Doctor |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 2007 May 24 |
| Publisher | |
| ISBN (Print) | 978-91-85559-67-1 |
| Publication status | Published - 2007 |
Bibliographical note
Defence detailsDate: 2007-05-24
Time: 13:00
Place: Lecture Hall Department of Obstetrics and Gynecology Lund University Sweden
External reviewer(s)
Name: Levine, Richard
Title: Professor
Affiliation: National Institutes of Health, Bethesda, USA
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<div class="article_info">Karl Kristensen, Veronica Lindström, Camilla Schmidt, Soren Blirup-Jensen, Anders Grubb and Dag Wide-Swensson. <span class="article_issue_date"></span>. <span class="article_title">Temporal changes of the plasma levels of cystatin C, Beta trace protein, Beta-2 microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process</span> <span class="journal_series_title">Scand J Clin Lab Invest.</span>, (inpress)</div>
<div class="article_info">Karl Kristensen, Dag Wide-Swensson, Camilla Schmidt, Soren Blirup-Jensen, Veronica Lindstrom, Helena Strevens and Anders Grubb. <span class="article_issue_date"></span>. <span class="article_title">Cystatin C, beta-2 microglobulin and beta trace protein in preeclampsia</span> <span class="journal_series_title">Acta Obstet Gynecol Scand.</span>, (inpress)</div>
<div class="article_info">Karl Kristensen, Irene Larsson and Stefan Hansson. <span class="article_issue_date">2007</span>. <span class="article_title">Increased cystatin C expression in the pre-eclamptic placenta</span> <span class="journal_series_title">Mol Hum Reprod</span>, <span class="journal_volume">vol 13</span> <span class="journal_pages">pp 189-195</span>.</div>
<div class="article_info">Karl Kristensen, Helena Strevens, Veronica Lindstrom, Anders Grubb and Dag Wide-Swensson. <span class="article_issue_date"></span>. <span class="article_title">Increased plasma levels of beta-2 microglobulin, cystatin C and beta trace protein in term pregnancy are not due to utero-placental production</span> <span class="journal_series_title">Int J Gynaecol Obstet.</span>, (submitted)</div>
<div class="article_info">Karl Kristensen, Dag Wide-Swensson, Veronica Lindstrom, Camilla Schmidt, Anders Grubb and Helena Strevens. <span class="article_issue_date"></span>. <span class="article_title">Serum amyloid A protein and C-reactive protein in normal pregnancy and in preeclampsia</span> <span class="journal_series_title">Int J Gynaecol Obstet.</span>, (accepted)</div>
Subject classification (UKÄ)
- Gynaecology, Obstetrics and Reproductive Medicine
Free keywords
- gynaecology
- andrology
- reproduction
- sexuality
- Obstetrik
- Obstetrics
- pregnancy
- renal function
- serum amyloid A protein
- Clinical chemistry
- Klinisk kemi
- preeclampsia
- beta-2 microglobulin
- C-reactive protein
- cystatin C
- inflammation
- placenta
- beta trace protein
- gynekologi
- andrologi
- reproduktion
- sexualitet