Identification of Proteomic Biomarkers of Preeclampsia in Amniotic Fluid Using SELDI-TOF Mass Spectrometry

Abstract

Objective: To identify proteomic biomarkers in amniotic fluid (AF) that can distinguish preeclampsia (PE) from chronic hypertension (CHTN) and normotensive controls (CTR). Methods: AF from women with PE, CHTN, and CTR were subjected to proteomic analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Results: Proteomic profiling of AF identified 2 biomarkers: peak X (17399.11 Da), which distinguished PE from CTR, and peak Y (28023.34 Da), which distinguished PE and CHTN from CTR. High performance liquid chromatography fractions containing the biomarkers were subjected to sodium dodecyl sulfate—polyacrylamide gel electrophoresis and in-gel tryptic digestion. The biomarkers were matched to proapolipoprotein A-I (peak Y) and a functionally obscure peptide, SBBI42 (peak X). Western blot analysis confirmed that AF from PE and CHTN had higher proapolipoprotein A-I levels than CTR. Conclusion: Proteomic analysis of AF can distinguish PE from CHTN and CTR. The discriminatory proteins were identified as proapolipoprotein A-I and SBBI42.

Keywords

Preeclampsia amniotic fluid SELDI proapolipoprotein A-I SBBI42.

Get full access to this article

View all access options for this article.

References

ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. 2002;99:159-167.

Higgins JR , de Swiet M. Blood-pressure measurement and classification in pregnancy. Lancet. 2001;357:131-135.

Zeek PM , Assali NS Vascular changes in the decidua associated with eclamptogenic toxemia of pregnancy . Am J Clin Pathol. 1950;20:1099-1109.

Sattar N. , Petrie JR , Jaap AJ The atherogenic lipoprotein phenotype and vascular endothelial dysfunction . Atherosclerosis. 1998;138:229-235.

Lorentzen B. , Henriksen T. Plasma lipids and vascular dysfunction in preeclampsia. Semin Reprod Endocrinol. 1998 ;16:33-39.

Sattar N. , Bendomir A. , Berry C. , Shepherd J. , Greer IA , Packard CJ Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis. Obstet Gynecol. 1997;89:403-408.

Papadopoulos MC , Abel PM , Agranoff D. , et al. A novel and accurate diagnostic test for human African trypanosomiasis. Lancet. 2004;363:1358-1363.

Puchades M. , Hansson SF , Nilsson CL , Andreasen N. , Blennow K. , Davidsson P. Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. Brain Res Mol Brain Res. 2003;118:140-146.

Davidsson P. , Sjogren M. , Andreasen N. , et al. Studies of the pathophysiological mechanisms in frontotemporal dementia by proteome analysis of CSF proteins . Brain Res Mol Brain Res. 2002;109:128-133.

10.

Weinberger SR , Morris TS , Pawlak M. Recent trends in protein biochip technology . Pharmacogenomics. 2000;1:395-416.

11.

Paweletz CP , Trock B. , Pennanen M. , et al. Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer. Dis Markers. 2001;17:301-307.

12.

Petricoin EF , Ardekani AM , Hitt BA , et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572-577.

13.

Ward DG , Suggett N. , Cheng Y. , et al. Identification of serum biomarkers for colon cancer by proteomic analysis. Br J Cancer. 2006;94:1898-1905.

14.

Davidsson P. , Westman-Brinkmalm A. , Nilsson CL , et al. Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients. Neuroreport. 2002;13:611-615.

15.

Gravett MG , Novy MJ , Rosenfeld RG , et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA. 2004;292:462-469.

16.

Weiner CP , Lee KY , Buhimschi CS , Christner R. , Buhimschi IA Proteomic biomarkers that predict the clinical success of rescue cerclage . Am J Obstet Gynecol. 2005;192:710-718.

17.

Buhimschi IA , Buhimschi CS , Weiner CP , et al. Proteomic but not enzyme-linked immunosorbent assay technology detects amniotic fluid monomeric calgranulins from their complexed calprotectin form. Clin Diagn Lab Immunol. 2005;12:837-844.

18.

Buhimschi IA , Christner R. , Buhimschi CS Proteomic biomarker analysis of amniotic fluid for identification of intraamniotic inflammation. BJOG. 2005;112:173-181.

19.

Park SJ , Yoon WG , Song JS , et al. Proteome analysis of human amnion and amniotic fluid by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proteomics. 2006;6:349-363.

20.

Buhimschi IA , Buhimschi CS , Christner R. , Weiner CP Proteomics technology for the accurate diagnosis of inflammation in twin pregnancies. BJOG. 2005;112:250-255.

21.

Ruetschi U. , Rosen A. , Karlsson G. , et al. Proteomic analysis using protein chips to detect biomarkers in cervical and amniotic fluid in women with intra-amniotic inflammation. J Proteome Res. 2005;4:2236-2242.

22.

Norwitz ER , Tsen LC , Park JS , et al. Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia. Am J Obstet Gynecol. 2005;193:957-964.

23.

Watanabe H. , Hamada H. , Yamada N. , et al. Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia. Proteomics. 2004;4:537-543.

24.

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-S22.

25.

Myers J. , Macleod M. , Reed B. , Harris N. , Mires G. , Baker P. Use of proteomic patterns as a novel screening tool in preeclampsia. J Obstet Gynaecol. 2004;24:873-874.

26.

Kashiwabara Y. , Onoyama Y. , Shimokawa H. , Hisanaga S. , Nakano H. A new method for measurement of surfactant specific apoprotein in amniotic fluid. Int J Gynaecol Obstet . 1989;29:147-152.

27.

Lara Gonzalez AL , Espinosa Perez C. , Tenorio R. , Garcia Alonso A. The induction of fetal lung maturity in preeclampsia. Ginecol Obstet Mex . 1999;67:295-299.

28.

Winn HN , Klosterman A. , Amon E. , Shumway JB , Artal R. Does preeclampsia influence fetal lung maturity? J Perinat Med. 2000;28:210-213.

29.

Bry K. , Lappalainen U. , Hallman M. Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth. J Clin Invest. 1997;99:2992-2999.

30.

Bry K. , Lappalainen U. , Hallman M. Cytokines and production of surfactant components. Semin Perinatol . 1996;20:194-205.

31.

Glumoff V. , Vayrynen O. , Kangas T. , Hallman M. Degree of lung maturity determines the direction of the interleukin-1-induced effect on the expression of surfactant proteins. Am J Respir Cell Mol Biol. 2000;22:280-288.

32.

Kashlan F. , Smulian J. , Shen-Schwarz S. , Anwar M. , Hiatt M. , Hegyi T. Umbilical vein interleukin 6 and tumor necrosis factor alpha plasma concentrations in the very preterm infant. Pediatr Infect Dis J. 2000;19:238-243.

33.

Shimoya K. , Matsuzaki N. , Taniguchi T. , et al. Interleukin-8 in cord sera: a sensitive and specific marker for the detection of preterm chorioamnionitis. J Infect Dis . 1992;165:957-960.

34.

Stallmach T. , Hebisch G. , Joller H. , Kolditz P. , Engelmann M. Expression pattern of cytokines in the different compartments of the feto-maternal unit under various conditions. Reprod Fertil Dev. 1995;7:1573-1580.

35.

Stallmach T. , Hebisch G. , Joller-Jemelka HI , Orban P. , Schwaller J. , Engelmann M. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease. Lab Invest. 1995; 73:384-392.

36.

Conrad KP , Miles TM , Benyo DF Circulating levels of immunoreactive cytokines in women with preeclampsia . Am J Reprod Immunol. 1998;40:102-111.

37.

KimyaY. , Akdis C. , Cengiz C. , et al. Plasma interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist levels in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 1997; 73:17-21.

38.

Kupferminc MJ , Peaceman AM , Dollberg S. , Socol ML Tumor necrosis factor-alpha is decreased in the umbilical cord plasma of patients with severe preeclampsia. Am J Perinatol. 1999;16:203-208.

39.

Munno I. , Chiechi LM , Lacedra G. , et al. Spontaneous and induced release of prostaglandins, interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha by placental tissue from normal and preeclamptic pregnancies. Am J Reprod Immunol. 1999;42:369-374.

40.

Schiff E. , Friedman SA , Baumann P. , Sibai BM , Romero R. Tumor necrosis factor-alpha in pregnancies associated with preeclampsia or small-for-gestational-age newborns. Am J Obstet Gynecol. 1994;170:1224-1229.

41.

Wang Y. , Baier J. , Adair CD , et al. Interleukin-8 stimulates placental prostacyclin production in preeclampsia. Am J Reprod Immunol. 1999;42:375-380.

42.

Wispe JR , Clark JC , Warner BB , et al. Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein.J Clin Invest. 1990;86:1954-1960.

43.

Romero R. , Vizoso J. , Emamian M. , et al. Clinical significance of liver dysfunction in pregnancy-induced hypertension. Am J Perinatol. 1988;5:146-151.

44.

Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy . Am J Obstet Gynecol. 1982;142:159-167.

45.

Matsuura T. , Koga S. , Ibayashi H. Increased proportion of proapolipoprotein A-I in HDL from patients with liver cirrhosis and hepatitis. Gastroenterol Jpn. 1988;23:394-400.

46.

Suehiro T. , Yamamoto M. , Yoshida K. , Ohno F. Increase of plasma proapolipoprotein A-I in patients with liver cirrhosis and its relationship to circulating high-density lipoproteins 2 and 3. Clin Chem. 1993;39:60-65.

47.

Isobe H. , Sakai H. , Satoh M. , Sakamoto S. , Koga S. , Nawata H. Decreased proapolipoprotein A-I processing in liver disease: evidence for hepatic participation in proapolipoprotein A-I conversion. Clin Chim Acta. 1990;189:303-311.

48.

Saku K. , Liu R. , Ohkubo K. , et al. In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) to apolipoprotein AI in rabbits. Biochim Biophys Acta. 1993;1167:257-263.

49.

Sliwkowski MB , Windmueller HG Rat liver and small intestine produce proapolipoprotein A-I which is slowly processed to apolipoprotein A-I in the circulation. J Biol Chem. 1984;259:6459-6465.

50.

Bojanovski D. , Gregg RE , Brewer HB Jr. Tangier disease. In vitro conversion of proapo-A-ITangier to mature APO-A-ITangier. J Biol Chem. 1984;259:6049-6051.

51.

Gratacos E. , Casals E. , Sanllehy C. , Cararach V. , Alonso PL , Fortuny A. Variation in lipid levels during pregnancy in women with different types of hypertension. Acta Obstet Gynecol Scand. 1996;75:896-901.

52.

Hubel CA , McLaughlin MK , Evans RW , Hauth BA , Sims CJ , Roberts JM Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum. Am J Obstet Gynecol. 1996;174:975-982.

53.

Ware-Jauregui S. , Sanchez SE , Zhang C. , Laraburre G. , King IB , Williams MA Plasma lipid concentrations in pre-eclamptic and normotensive Peruvian women. Int J Gynaecol Obstet. 1999;67:147-155.

54.

Manten GT , van der Hoek YY , Marko Sikkema J. , et al. The role of lipoprotein (a) in pregnancies complicated by preeclampsia . Med Hypotheses. 2005;64:162-169.

55.

Cekmen MB , Erbagci AB , Balat A. , et al. Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension. Clin Biochem. 2003;36:575-578.

56.

Winkler K. , Wetzka B. , Hoffmann MM , et al.Triglyceride-rich lipoproteins are associated with hypertension in preeclampsia. J Clin Endocrinol Metab. 2003;88:1162-1166.

57.

Bayhan G. , KocyigitY, Atamer A. , AtamerY, Akkus Z. Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia. Gynecol Endocrinol . 2005;21:1-6.

58.

Belo L. , Caslake M. , Gaffney D. , et al. Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis. 2002;162:425-432.