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PLASMA PROTEINS IN NORMAL AND PREECLAMPTIC PREGNANCY

Kristensen, Karl LU (2007) In Lund University, Faculty of Medicine Doctoral Dissertation 2007:89.
Abstract (Swedish)
Popular Abstract in Swedish

Havandeskapsförgiftning (preeklampsi) är ett allvarligt risktillstånd som uppkommer vid 1.5-2.0 % av alla graviditeter och sjukdomen är en av de största orsakerna till mödra- och barndödlighet i världen. Preeklampsi karaktäriseras av högt blodtryck och läckage av äggvita i urinen under sista hälften av graviditeten hos en tidigare frisk kvinna. Njurarna spelar en avgörande roll i utvecklingen av dessa symptom. Obehandlat kan tillståndet medföra att kvinnan drabbas av allvarliga komplikationer som njur- och leversvikt, blödningsrubbningar och kramper (eklampsi). Barnet kan drabbas av tillväxthämning, syrebrist och död. Trots intensiv forskning är orsaken till preeklampsi fortfarande till stor del... (More)
Popular Abstract in Swedish

Havandeskapsförgiftning (preeklampsi) är ett allvarligt risktillstånd som uppkommer vid 1.5-2.0 % av alla graviditeter och sjukdomen är en av de största orsakerna till mödra- och barndödlighet i världen. Preeklampsi karaktäriseras av högt blodtryck och läckage av äggvita i urinen under sista hälften av graviditeten hos en tidigare frisk kvinna. Njurarna spelar en avgörande roll i utvecklingen av dessa symptom. Obehandlat kan tillståndet medföra att kvinnan drabbas av allvarliga komplikationer som njur- och leversvikt, blödningsrubbningar och kramper (eklampsi). Barnet kan drabbas av tillväxthämning, syrebrist och död. Trots intensiv forskning är orsaken till preeklampsi fortfarande till stor del okänd. Det enda sättet att häva tillståndet är genom att avsluta graviditeten med förlossning av barn och moderkaka.



Målsättningen med vår forskning är att öka kunskapen kring ett antal biokemiska markörer som skulle kunna användas i den medicinska utredningen och övervakningen av gravida med tecken till preeklampsi. I avhandlingen karaktäriseras plasmaproteinerna beta-2 microglobulin (B2M), cystatin C, beta trace protein (BTP), C-reactive protein och serum amyloid A protein hos gravida med och utan preeklampsi. Plasmanivån av B2M, cystatin C och BTP avspeglar njurarnas filtrationsförmåga hos icke-gravida. C-reactive protein och serum amyloid A protein är känsliga inflammationsmarkörer.



Trots en ökad filtration i njurarna redan tidigt i graviditeten visade sig plasmanivåerna av B2M, cystatin C och BTP vara i stort sett oförändrade under första och andra trimestern, men förhöjda med 20-40 % under tredje trimestern. Detta beror sannolikt på en ändrad filtration i njurarna i sen graviditet. Vid preeklampsi var nivåerna av dessa proteiner ännu högre, vilket kan avspegla en försämring av njurfunktionen. Således är dessa plasmaproteiner potentiella markörer för att diagnostisera preeklampsi och för att övervaka njurfunktionen vid preeklampsi.



Cystatin C fungerar som en hämmare av proteaser, en rad enzymer som bryter ned proteiner, och kan ha betydelse för moderkakans utveckling och funktion. Produktionen av cystatin C i moderkakan är förhöjd vid preeklampsi och skulle teoretiskt sett även kunna bidra till den förhöjda plasmanivån av proteinet i sen graviditet och vid preeklampsi. Vid jämförelse av plasmanivån av cystatin C från venöst blod från livmodern och plasmanivån av proteinet från perifert venöst blod vid slutet av den normala graviditeten, fann vi emellertid ingen skillnad. Detta tyder på att moderkakans och livmoderns produktion av cystatin C vid normal graviditet inte bidrar till den ökade plasmanivån i någon större grad.



Plasmanivån av C-reactive protein och serum amyloid A protein visade sig inte vara förhöjd hos kvinnor med preeklampsi jämfört med normala gravida. Det inflammatoriska tillstånd som har föreslagits ligga bakom preeklampsi avspeglas således inte av dessa inflammationsmarkörer.



En förbättrad övervakning av njurfunktionen vid suspekt och manifest preeklampsi med hjälp av de biokemiska markörerna B2M, cystatin C och BTP skulle kunna öka den diagnostiska säkerheten och minska risken för allvarliga komplikationer för moder och barn. (Less)
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,... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Levine, Richard, National Institutes of Health, Bethesda, USA
organization
publishing date
type
Thesis
publication status
published
subject
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
in
Lund University, Faculty of Medicine Doctoral Dissertation
volume
2007:89
pages
74 pages
publisher
Department of Obstetrics and Gynecology, Lund University
defense location
Lecture Hall Department of Obstetrics and Gynecology Lund University Sweden
defense date
2007-05-24 13:00
ISSN
1652-8220
ISBN
978-91-85559-67-1
language
English
LU publication?
yes
id
0f066d21-e530-4713-8c3b-a99b6b6753b1 (old id 548649)
date added to LUP
2007-09-12 08:25:34
date last changed
2016-09-19 08:44:55
@phdthesis{0f066d21-e530-4713-8c3b-a99b6b6753b1,
  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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.},
  author       = {Kristensen, Karl},
  isbn         = {978-91-85559-67-1},
  issn         = {1652-8220},
  keyword      = {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},
  language     = {eng},
  pages        = {74},
  publisher    = {Department of Obstetrics and Gynecology, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation},
  title        = {PLASMA PROTEINS IN NORMAL AND PREECLAMPTIC PREGNANCY},
  volume       = {2007:89},
  year         = {2007},
}