American Journal of Obstetrics & Gynecology
Volume 199, Issue 5 , Pages 551.e1-551.e16 , November 2008

Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia

  • Irina A. Buhimschi, MD

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT
    • Corresponding Author InformationReprints: Irina A. Buhimschi, MD, Department of Obstetrics, Gynecology, and Reproductive Science, Yale University School of Medicine, 333 Cedar St, LCI 804, PO Box 208063, New Haven, CT 06520-8063
    • ,
  • Guomao Zhao, BSc

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT
    • ,
  • Edmund F. Funai, MD

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT
    • ,
  • Nathan Harris, MSc

      Affiliations

    • Ciphergen Biosystems, Inc, Fremont, CA
    • ,
  • Isaac E. Sasson, MD

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT
    • ,
  • Ira M. Bernstein, MD

      Affiliations

    • Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT
    • ,
  • George R. Saade, MD

      Affiliations

    • Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
    • ,
  • Catalin S. Buhimschi, MD

      Affiliations

    • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT

Received 15 December 2007 ,Revised 12 April 2008 ,Accepted 3 July 2008.

References 

  1. Sibai BM, Ewell M, Levine RJ, et al. Risk factors associated with preeclampsia in healthy nulliparous women: the Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol. 1997;177:1003–1010
  2. Samadi AR, Mayberry RM, Zaidi AA, Pleasant JC, McGhee N, Rice RJ. Maternal hypertension and associated pregnancy complications among African-American and other women in the United States. Obstet Gynecol. 1996;87:557–563
  3. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynecol. 1988;158:80–83
  4. MacKay AP, Berg CJ, Duran C, Chang J, Rosenberg H. An assessment of pregnancy-related mortality in the United States. Paediatr Perinat Epidemiol. 2005;19:206–214
  5. Fronterhouse W, Christensen FC, Rayburn LA, Gilson GJ, Curet LB, Rayburn WF. Mandated preterm delivery: its prevalence and impact at a tertiary referral center. J Matern Fetal Med. 2001;10:162–165
  6. Ananth CV, Vintzileos AM. Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med. 2006;19:773–782
  7. 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
  8. Buhimschi IA, Saade GR, Chwalisz K, Garfield RE. The nitric oxide pathway in pre-eclampsia: pathophysiological implications. Hum Reprod Update. 1998;4:25–42
  9. Zamorski MA, Green LA. NHBPEP report on high blood pressure in pregnancy: a summary for family physicians. Am Fam Physician. 2001;64:263–270
  10. Wilkins MR, Sanchez JC, Gooley AA, et al. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol Genet Eng Rev. 1996;13:19–50
  11. Lindheimer MD, Katz AI. The normal and diseased kidney in pregnancy. In:  Schrier RW editors. Diseases of the kidney and urinary tract. 7th ed.. Philadelphia: Lippincott, Williams and Wilkins; 2001;p. 2129–2165
  12. Ferrazzani S, Caruso A, De Carolis S, Martino IV, Mancuso S. Proteinuria and outcome of 444 pregnancies complicated by hypertension. Am J Obstet Gynecol. 1990;162:366–371
  13. Silkensen JR, Kasiske BL. Laboratory assessment of kidney disease: clearance, urinalysis, and kidney biopsy. In:  Brenner BM editors. The kidney. 7th ed.. Philadelphia: WB Saunders; 2004;p. 1107
  14. Buhimschi CS, Norwitz ER, Funai E, et al. Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia. Am J Obstet Gynecol. 2005;192:734–741
  15. Zhou XH, Obuchowski NA, McClish DK. Statistical methods in diagnostic medicine. New York: John Wiley & Sons; 2002;
  16. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem. 2005;51:1577–1586
  17. Levine RJ, Thadhani R, Qian C, et al. Urinary placental growth factor and risk of preeclampsia. JAMA. 2005;293:77–85
  18. Buhimschi CS, Magloire L, Funai E, et al. Fractional excretion of angiogenic factors in women with severe preeclampsia. Obstet Gynecol. 2006;107:1103–1113
  19. Weinstein S, Obuchowski NA, Lieber ML. Clinical evaluation of diagnostic tests. Am J Roentgenol. 2005;184:14–19
  20. Lindheimer MD, Davison JM. Renal biopsy during pregnancy: ‘to b... or not to b…?’. Br J Obstet Gynaecol. 1987;94:932–934
  21. Buhimschi IA, Christner R, Buhimschi CS. Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation. BJOG. 2005;112:173–181
  22. Buhimschi CS, Weiner CP, Buhimschi IA. Clinical proteomics Part II (The emerging role of proteomics over genomics in spontaneous preterm labor/birth). Obstet Gynecol Survey. 2006;61:543–553
  23. Buhimschi IA, Buhimschi C. Proteomics of the amniotic fluid in assessment of the placenta (Relevance for preterm birth). Placenta. 2008;29(Suppl A):S95–S101
  24. Merchant M, Weinberger S. Recent advancements in surface enhanced laser desorption/ionization time of flight mass spectrometry. Electrophoresis. 2000;21:1164–1167
  25. Cronbach L. Coefficient alpha and the internal structure of tests. Psychometrika. 1951;16:297–333
  26. Fleiss JL, Cuzick J. The reliability of dichotomous judgements: unequal numbers of judges per subject. Applied Psychological Measurement. 1979;3:537–542
  27. Carrell RW, Jeppsson JO, Laurell CB, et al. Structure and variation of human alpha 1-antitrypsin. Nature. 1982;298:329–334
  28. Callea F, Brisigotti M, Faa G, Lucini L, Eriksson S. Identification of PiZ gene products in liver tissue by a monoclonal antibody specific for the Z mutant of alpha 1-antitrypsin. J Hepatol. 1991;12:372–376
  29. Janciauskiene S, Dominaitiene R, Sternby NH, Piitulainen E, Eriksson S. Detection of circulating and endothelial cell polymers of Z and wild type alpha 1-antitrypsin by a monoclonal antibody. J Biol Chem. 2002;277:26540–26546
  30. James EL, Whisstock JC, Gore MG, Bottomley SP. Probing the unfolding pathway of alpha 1-antitrypsin. J Biol Chem. 1999;274:9482–9488
  31. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br J Obstet Gynaecol. 1992;99:547–553
  32. Chan P, Brown M, Simpson JM, Davis G. Proteinuria in pre-eclampsia: how much matters?. BJOG. 2005;112:280–285
  33. Ferrazzani S, Caruso A, De Carolis S, Martino IV, Mancuso S. Proteinuria and outcome of 444 pregnancies complicated by hypertension. Am J Obstet Gynecol. 1990;162:366–371
  34. Brown MA, Buddle ML. Inadequacy of dipstick proteinuria in hypertensive pregnancy. Aust N Z J Obstet Gynaecol. 1995;35:366–369
  35. Rodriguez-Thompson D, Lieberman ES. Use of a random urinary protein to creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Am J Obstet Gynecol. 2001;185:808–811
  36. Meyer NL, Mercer BM, Friedman SA, Sibai BM. Urinary dipstick protein: a poor predictor of absent or severe proteinuria. Am J Obstet Gynecol. 1994;170:137–141
  37. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2001;20:IX–XIV
  38. Coakley RJ, Taggart C, O'Neill S, McElvaney NG. Alpha 1-antitrypsin deficiency: biological answers to clinical questions. Am J Med Sci. 2001;321:33–41
  39. Lisowska-Myjak B. AAT as a diagnostic tool. Clin Chim Acta. 2005;352:1–13
  40. Carrell RW. Alpha 1-antitrypsin: molecular pathology, leukocytes, and tissue damage. J Clin Invest. 1986;78:1427–1431
  41. Bergman D, Kadner SS, Cruz MR, et al. Synthesis of alpha 1-antichymotrypsin and alpha 1-antitrypsin by human trophoblast. Pediatr Res. 1993;34:312–317
  42. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. Glycoprotein (orosomucoid), alpha 1-antitrypsin, and haptoglobin: a comparison of a large cohort to the world's literature. J Clin Lab Anal. 2000;14:265–270
  43. Engstrom G, Janzon L, Berglund G, et al. Blood pressure increase and incidence of hypertension in relation to inflammation-sensitive plasma proteins. Arterioscler Thromb Vasc Biol. 2002;22:2054–2058
  44. Engstrom G, Lind P, Hedblad B, Stavenow L, Janzon L, Lindgarde F. Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke. Stroke. 2002;33:2744–2749
  45. Schmaier AH. The plasma kallikrein-kinin system counterbalances the renin-angiotensin system. J Clin Invest. 2002;109:1007–1009
  46. Janciauskiene S, Moraga F, Lindgren S. C-terminal fragment of alpha 1-antitrypsin activates human monocytes to a pro-inflammatory state through interactions with the CD36 scavenger receptor and LDL receptor. Atherosclerosis. 2001;158:41–51
  47. Kupferminc MJ, Peaceman AM, Wigton TR, Rehnberg KA, Socol ML. Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecol. 1994;170:1752–1757
  48. Aguzzi A, Haass C. Games played by rogue proteins in prion disorders and Alzheimer's disease. Science. 2003;302:814–818
  49. Matheson NR, Wong PS, Travis J. Enzymatic inactivation of human alpha-1-proteinase inhibitor by neutrophil myeloperoxidase. Biochem Biophys Res Commun. 1979;88:402–409
  50. Lomas DA, Belorgey D, Mallya M, et al. Polymerisation underlies alpha 1-antitrypsin deficiency, dementia and other serpinopathies. Front Biosci. 2004;9:2873–2891
  51. Gudehithlu KP, Pegoraro AA, Dunea G, Arruda JA, Singh AK. Degradation of albumin by the renal proximal tubule cells and the subsequent fate of its fragments. Kidney Int. 2004;65:2113–2122
  52. Travis J, Shieh BH, Potempa J. The functional role of acute phase plasma proteinase inhibitors. Tokai J Exp Clin Med. 1988;13:313–320
  53. Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005;6:11–22

 This study was supported by the Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, and partially supported by funds from the Department of Health and Human Services Grant R01 HD 047321-01 (to I.A.B.).

 Financial disclosure statement: Drs Irina and Catalin Buhimschi are joint inventors on patent applications filed by Yale University regarding the use of urinary angiogenic factors and proteomic profiling for diagnosis of preeclampsia. Dr Nathan Harris is an employee of Ciphergen Biosystems. Drs Irina Buhimschi and Catalin Buhimschi have no financial relationship with Ciphergen Biosystems and have collaborated with Mr Harris on a solely scientific basis. None of the other authors has any financial relationships regarding the content of this manuscript. Role of the funding source: none of the funding sources had any involvement in study design, interpretation of data, writing of the report, or the decision to submit the paper for publication.

 Cite this article as: Buhimschi IA, Zhao G, Funai EF, et al. Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia. Am J Obstet Gynecol 2008;199:551.e1-551.e16.

PII: S0002-9378(08)00790-4

doi: 10.1016/j.ajog.2008.07.006

American Journal of Obstetrics & Gynecology
Volume 199, Issue 5 , Pages 551.e1-551.e16 , November 2008

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