Hindawi Publishing Corporation
Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 305964, 8 pages
doi:10.1155/2012/305964
Research Article
Quantitative Proteomic (iTRAQ) Analysis of 1st Trimester
Maternal Plasma Samples in Pregnancies at Risk for Preeclampsia
Varaprasad Kolla,
1
Paul Jen¨ o,
2
Suzette Moes,
2
Olav Lapaire,
1
Irene Hoesli,
1
and Sinuhe Hahn
1, 3
1
Department of Biomedicine, University Women’s Hospital, 4031 Basel, Switzerland
2
Biozentrum, University of Basel, 4056 Basel, Switzerland
3
Laboratory for Prenatal Medicine, Department of Biomedicine, University Women’s Hospital, Hebelstrasse 20,
CH 4031 Basel, Switzerland
Correspondence should be addressed to Sinuhe Hahn, shahn@uhbs.ch
Received 31 May 2011; Revised 26 December 2011; Accepted 28 December 2011
Academic Editor: Saulius Butenas
Copyright © 2012 Varaprasad Kolla et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative
proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma
biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether
this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma
samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated
deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared
to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels
of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding
protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for
the detection of new preeclampsia screening markers.
1. Introduction
Preeclampsia is a major health concern, as it is a leading cause
of fetal and maternal mortality and morbidity, worldwide
[1]. A major clinical deficit is that no reliable screening
markers exist to detect at-risk pregnancies, thereby offering
no opportunity for intervening therapies prior to the onset of
symptoms [2, 3]. This is especially relevant for severe cases of
early onset forms of the disorder, resulting in the delivery of
premature babies, who are frequently affected by intrauterine
growth retardation.
It is widely accepted that the underlying aetiology of this
enigmatic disorder, characterised by sudden hypertension in
previously normotensive pregnant women, involves the pla-
centa. In this context, the placentae of early onset preeclamp-
sia are usually characterised by abnormalities in trophoblast
differentiation, lack of modification of the maternal spiral
arteries, and ill-defined villous structure [4].
Recent studies have indicated that the clinical symptoms,
such as hypertension and proteinuria, are largely brought
about by alterations in the levels of angiogenic factors
produced by the placenta such as placental growth factor
(PIGF), vascular endothelial growth factor (VEGF), soluble
Flt-1, and endoglin [5, 6] Although alterations in the levels
of these cytokines do precede the onset of clinical symptoms,
it is not clear how effective they will be as screening markers,
as these changes occur relatively late in gestation.
A considerable effort in prenatal medicine is being de-
voted to the development of efficacious first trimester screen-
ing tools, to detect pregnancies at risk for fetal aneuploidies,
but also pregnancy-related disorders such as preeclampsia,
as this would permit sufficient time for intervention. In this