A Mass Spectrometric Multicenter Study Supports Classification of Preeclampsia as Heterogeneous Disorder

Objective. The diagnostic value of affinity-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis to distinguish preeclampsia (PE) from matched controls was tested in a multicenter setting. Methods. Serum samples of preeclamptic (n = 60) and healthy pregnant women (n = 66) from four centers were prospectively analyzed with predefined rule sets. Results. Overall sample classification reached sensitivity of 0.88 and specificity of 0.73. Separate calculations for early-onset PEs only (before 34 weeks of gestation) revealed sensitivity of 0.88 and specificity of 0.89. Conclusion. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry serum-profiling with center-wise standardization offers a fast and robust method to classify PE and contributes to the theory of PE being a heterogeneous disorder that ought to be subclassified.

[1]  J. García-Erce,et al.  [HELLP syndrome]. , 2002, Medicina clinica.

[2]  M. Glocker,et al.  Mass spectrometric protein structure characterization reveals cause of migration differences of haptoglobin α chains in two‐dimensional gel electrophoresis , 2004, Proteomics.

[3]  J. Kingdom,et al.  Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia/intrauterine growth restriction. , 2006, American journal of obstetrics and gynecology.

[4]  M. Glocker,et al.  Differentiation of HELLP patients from healthy pregnant women by proteome analysis--on the way towards a clinical marker set. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[5]  L. Magee,et al.  Subclassification of Preeclampsia , 2003, Hypertension in pregnancy.

[6]  Magnus Palmblad,et al.  Mass spectrometry in clinical proteomics – from the present to the future , 2008, Proteomics. Clinical applications.

[7]  K. Lim,et al.  Circulating angiogenic factors and the risk of preeclampsia. , 2004, The New England journal of medicine.

[8]  I. Sargent,et al.  Preeclampsia: an excessive maternal inflammatory response to pregnancy. , 1999, American journal of obstetrics and gynecology.

[9]  Steven H. Wu,et al.  A proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease , 2009, Proteomics.

[10]  M. Skinner,et al.  Identification of S‐sulfonation and S‐thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis , 2003, Protein science : a publication of the Protein Society.

[11]  B. Gharesi-Fard,et al.  Proteome differences of placenta between pre-eclampsia and normal pregnancy. , 2010, Placenta.

[12]  B. Huppertz.  Placental Origins of Preeclampsia: Challenging the Current Hypothesis , 2008, Hypertension.

[13]  C. Metz.  Basic principles of ROC analysis. , 1978, Seminars in nuclear medicine.

[14]  Jean-Marie Moutquin,et al.  The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP) , 2001, Hypertension in pregnancy.

[15]  T. Arinami,et al.  Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia , 2004, Proteomics.

[16]  I. Sargent,et al.  Pre-eclampsia, the placenta and the maternal systemic inflammatory response--a review. , 2003, Placenta.

[17]  I. Sargent,et al.  Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. , 1999, Clinical chemistry.

[18]  B. Sibai,et al.  Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. , 2006, The New England journal of medicine.

[19]  D. Schlembach.  Pre-eclampsia--still a disease of theories. , 2003, Fukushima journal of medical science.

[20]  M. Glocker,et al.  Multifactorial analysis of affinity-mass spectrometry data from serum protein samples: A strategy to distinguish patients with preeclampsia from matching control individuals , 2010, Journal of the American Society for Mass Spectrometry.

[21]  J. Kingdom,et al.  Macrophage-Induced Apoptosis Limits Endovascular Trophoblast Invasion in the Uterine Wall of Preeclamptic Women , 2001, Laboratory Investigation.

[22]  F. Ghezzi,et al.  Disturbed Feto‐Maternal Cell Traffic in Preeclampsia , 1998, Obstetrics and gynecology.

[23]  Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. , 2000, American journal of obstetrics and gynecology.

[24]  M. Glocker,et al.  Cryodetector mass spectrometry profiling of plasma samples for HELLP diagnosis: An exploratory study , 2005, Proteomics.

[25]  K. Nicolaides,et al.  A novel approach to first‐trimester screening for early pre‐eclampsia combining serum PP‐13 and Doppler ultrasound , 2005, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[26]  G. Howlett,et al.  Metabolism of prealbumin in rats and changes induced by acute inflammation. , 1982, European journal of biochemistry.

[27]  J. Dudenhausen,et al.  An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. , 2010, American journal of obstetrics and gynecology.

[28]  C. Redman,et al.  Women with Preeclampsia Have Increased Serum Levels of Pregnancy‐Associated Plasma Protein A (PAPP‐A), Inhibin A, Activin A and Soluble E‐selectin , 2003, Hypertension in pregnancy.

[29]  N. Groome,et al.  Activin A and inhibin A as possible endocrine markers for pre-eclampsia , 1997, The Lancet.

[30]  B. Huppertz,et al.  Longitudinal Determination of Serum Placental Protein 13 during Development of Preeclampsia , 2008, Fetal Diagnosis and Therapy.

[31]  C. Hubel,et al.  The two stage model of preeclampsia: variations on the theme. , 2009, Placenta.

[32]  C. Garlanda,et al.  Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and intrauterine growth restriction. , 2006, American journal of obstetrics and gynecology.

[33]  James J. Walker,et al.  Pre-eclampsia , 2000, The Lancet.

[34]  K. Harrington,et al.  Second-trimester maternal serum inhibin A concentration as an early marker for preeclampsia. , 1999, American journal of obstetrics and gynecology.

[35]  G. Saade,et al.  Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia. , 2008, American journal of obstetrics and gynecology.