Home Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification
Article
Licensed
Unlicensed Requires Authentication
Article has an altmetric score of 1

Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification

  • Yoshihiko Araki ORCID logo EMAIL logo , Yoshiki Miura and Hiroshi Fujiwara
Published/Copyright: October 19, 2021
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 60 Issue 1

Abstract

Among the many complications associated with pregnancy, hypertensive disorders of pregnancy (HDP) constitute one of the most important. Since the pathophysiology of HDP is complex, new disease biomarkers (DBMs) are needed to serve as indicators of disease activity. However, in the current status of laboratory medicine, despite the fact that blood pressure measurement has been used for a long time, not many DBMs contribute adequately to the subsequent diagnosis and treatment. In this article, we discuss studies focusing on peptide fragments in blood identified by comprehensive quantitative methods, among the currently proposed DBM candidates. Furthermore, we describe the basic techniques of peptidomics, especially quantitative proteomics, and outline the current status and challenges of measuring peptides in blood as DBM for HDP.

Keywords: disease biomarker; hypertensive disorders of pregnancy; peptidomics; quantitative proteomics
Corresponding author: Yoshihiko Araki, MD DMedSci, Institute for Environmental & Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan; Department of Obstetrics & Gynecology, Juntendo University Graduate School of Medicine, Tokyo, Japan; and Department of Pathology and Microbiology, Division of Microbiology and Immunology, Nihon University School of Medicine, Tokyo, Japan, E-mail:

Funding source: The Japan Society for the Promotion of Science

Award Identifier / Grant number: 25462575/16K11111/17K19734/17K19719/19K22681/18KK0256

Funding source: Japan Science and Technology Agency

Award Identifier / Grant number: AS2311641F/19-191030923

Funding source: The Ministry of Education, Culture, Sports, Science and Technology, Japan

Award Identifier / Grant number: “High-Tech Research Center” Project for Private Universities: matching fund subsidy

Funding source: The Japan Agency for Medical Research and Development

Award Identifier / Grant number: 17gk0110024h0001/17cm0106XXXh0001

Acknowledgments

We would like to thank all collaborators who contributed to the MS analysis and related studies.

  1. Research funding: This work was supported in part by Grants-in Aid for Scientific Research Nos. 25462575/16K11111, for Challenging Research Nos. 17K19734/17K19719/19K22681, and for Fostering Joint International Research No. 18KK0256 from the Japan Society for the Promotion of Science (JSPS), grants Nos. 17gk0110024h0001/17cm0106XXXh0001 from the Japan Agency for Medical Research and Development (AMED), grants No. AS2311641F/19-191030923 from Japan Science and Technology Agency, and “High-Tech Research Center” Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

  2. Author contributions: Y.A., Y.M., and H.F. conceived, designed, and directed the study, provided financial supports, and wrote the article. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

References

1. Nelson-Piercy, C, de Swiet, M, Lewis, G. Medical deaths in pregnancy. Clin Med 2008;8:11–2. https://doi.org/10.7861/clinmedicine.8-1-11.Search in Google Scholar

2. de Swiet, M. Maternal mortality in the developed world: lessons from the UK confidential enquiry. Obstet Med 2008;1:7–10. https://doi.org/10.1258/om.2008.080020.Search in Google Scholar

3. von Dadelszen, P, Payne, B, Li, J, Ansermino, JM, Broughton Pipkin, F, Côté, AM, et al.. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet 2011;377:219–27. https://doi.org/10.1016/s0140-6736(10)61351-7.Search in Google Scholar

4. Brown, MA, Magee, LA, Kenny, LC, Karumanchi, SA, McCarthy, FP, Saito, S, et al.. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension 2018;72:24–43. https://doi.org/10.1161/hypertensionaha.117.10803.Search in Google Scholar PubMed

5. Sutton, ALM, Harper, LM, Tita, ATN. Hypertensive disorders in pregnancy. Obstet Gynecol Clin N Am 2018;45:333–47. https://doi.org/10.1016/j.ogc.2018.01.012.Search in Google Scholar PubMed

6. Haram, K, Svendsen, E, Abildgaard, U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth 2009;9:8. https://doi.org/10.1186/1471-2393-9-8.Search in Google Scholar PubMed PubMed Central

7. Wallace, K, Harris, S, Addison, A, Bean, C. HELLP syndrome: pathophysiology and current therapies. Curr Pharmaceut Biotechnol 2018;19:816–26. https://doi.org/10.2174/1389201019666180712115215.Search in Google Scholar PubMed

8. Araki, Y, Nonaka, D, Hamamura, K, Yanagida, M, Ishikawa, H, Banzai, M, et al.. Clinical peptidomic analysis by a one-step direct transfer technology: its potential utility for monitoring of pathophysiological status in female reproductive system disorders. J Obstet Gynaecol Res 2013;39:1440–8. https://doi.org/10.1111/jog.12140.Search in Google Scholar PubMed

9. Araki, Y, Yanagida, M. Hypertensive disorders of pregnancy: strategy to develop clinical peptide biomarkers for more accurate evaluation of the pathophysiological status of this syndrome. In: Makowski, GS, editor. Advances in clinical chemistry. London, UK: Elsevier; 2020, vol 94:1–30 pp.10.1016/bs.acc.2019.07.007Search in Google Scholar PubMed

10. Taylor, RN. Review: immunobiology of preeclampsia. Am J Reprod Immunol 1997;37:79–86. https://doi.org/10.1111/j.1600-0897.1997.tb00195.x.Search in Google Scholar PubMed

11. Salas, SP. What causes pre-eclampsia? Bailliere Best Pract Res Clin Obstet Gynaecol 1999;13:41–57. https://doi.org/10.1053/beog.1999.0005.Search in Google Scholar

12. Cetin, A. Eclampsia. In: advanced therapy. In: Mohler, ER III, Townsend, RR, editors. Hypertension and vascular disease. Hamilton, OT, Canada: BC Decker Inc; 2006:407–15 pp.Search in Google Scholar

13. Lindheimer, MD, Roberts, JM, Cunningham, FG, Chesley, L. Introduction, history, controversies, and definitions. In: Lindheimer, MD, Roberts, JM, Cunningham, FG, editors. Chesley’s hypertensive disorders in pregnancy, 3rd ed. Burlington, MA, USA: Elsevier; 2009:1–23 pp.10.1016/B978-0-12-374213-1.00001-XSearch in Google Scholar

14. Bell, MJ. A historical overview of preeclampsia-eclampsia. J Obstet Gynecol Neonatal Nurs 2010;39:510–8. https://doi.org/10.1111/j.1552-6909.2010.01172.x.Search in Google Scholar

15. Itoh, Y. Clinical research and tests on urinary protein: its past, present and future. Jpn J Electroph 1997;41:325–8. [in Japanese]. https://doi.org/10.2198/sbk.41.325.Search in Google Scholar

16. West, JB. Stephan Hales: neglected respiratory physiologist. J Appl Physiol Respir Environ Exerc Physiol 1984;57:635–9. https://doi.org/10.1152/jappl.1984.57.3.635.Search in Google Scholar

17. Roguin, A. Scipione Riva-Rocci and the men behind the mercury sphygmomanometer. Int J Clin Pract 2006;60:73–9. https://doi.org/10.1111/j.1742-1241.2005.00548.x.Search in Google Scholar

18. Korotkov, NS. Concerning the problem of the methods of blood pressure measurement. J Hypertens 2005;3:5 (translated in English from original article from Proceeding of the Emperor’s Military Medical Academy St Petersburg 1905;11:365 [in Russian]). https://doi.org/10.1097/00004872-200501000-00003.Search in Google Scholar

19. Savino, R, Paduano, S, Preianò, M, Terracciano, R. The proteomics big challenge for biomarkers and new drug-targets discovery. Int J Mol Sci 2012;13:13926–48. https://doi.org/10.3390/ijms131113926.Search in Google Scholar

20. Richter, R, Schulz-Knappe, P, Schrader, M, Ständker, L, Jürgens, M, Tammen, H, et al.. Composition of the peptide fraction in human blood plasma: database of circulating human peptides. J Chromatogr B Biomed Sci Appl 1999;726:25–35. https://doi.org/10.1016/s0378-4347(99)00012-2.Search in Google Scholar

21. Van, JA, Scholey, JW, Konvalinka, A. Insights into diabetic kidney disease using urinary proteomics and bioinformatics. J Am Soc Nephrol 2017;28:1050–61. https://doi.org/10.1681/asn.2016091018.Search in Google Scholar

22. Greening, DW, Kapp, EA, Simpson, RJ. The peptidome comes of age: mass spectrometry-based characterization of the circulating cancer peptidome. Enzymes 2017;42:27–64. https://doi.org/10.1016/bs.enz.2017.08.003.Search in Google Scholar PubMed

23. Tanaka, K, Tsugawa, N, Kim, Y-O, Sanuki, N, Takeda, U, Lee, L-J. A new rapid and comprehensive peptidome analysis by one-step direct transfer technology for 1-D elecrophoresis/MALDI mass spectrometry. Biochem Biophys Res Commun 2009;379:110–4. https://doi.org/10.1016/j.bbrc.2008.12.016.Search in Google Scholar PubMed

24. Araki, Y, Nonaka, D, Tajima, A, Maruyama, M, Nitto, T, Ishikawa, H, et al.. Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension. Proteomics 2011;11:2727–37. https://doi.org/10.1002/pmic.201000753.Search in Google Scholar PubMed

25. Hamamura, K, Nonaka, D, Ishikawa, H, Banzai, M, Yoshitake, H, Yanagida, M, et al.. Simple quantitation for potential serum disease biomarker peptides, primarily identified by a peptidomics approach in the serum with hypertensive disorders of pregnancy. Ann Clin Biochem 2016;53:85–96. https://doi.org/10.1177/0004563215583697.Search in Google Scholar PubMed

26. Hamamura, K, Yanagida, M, Ishikawa, H, Banzai, M, Yoshitake, H, Nonaka, D, et al.. Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multi-dimensional peptide analysis in women with pregnancy induced hypertension. Ann Clin Biochem 2018;55:287–95. https://doi.org/10.1177/0004563217717748.Search in Google Scholar PubMed

27. Yanagida, M, Hamamura, K, Takamori, K, Araki, Y. The simultaneous quantification of candidate serum biomarker peptides for hypertensive disorders of pregnancy. Ann Clin Biochem 2019;56:457–65. https://doi.org/10.1177/0004563219839084.Search in Google Scholar PubMed

28. Araki, Y. Commentary on a “strategy to develop clinical peptide biomarkers for more accurate evaluation of the pathophysiological status of hypertensive disorders of pregnancy”. Clin Mother Child Health 2020;17:373.10.1016/bs.acc.2019.07.007Search in Google Scholar

29. Ross, PL, Huang, YN, Marches, JN, Williamson, B, Parker, K, Hattan, S, et al.. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 2004;3:1154–69. https://doi.org/10.1074/mcp.m400129-mcp200.Search in Google Scholar

30. Thompson, A, Schäfer, J, Kuhn, K, Kienle, S, Schwarz, J, Schmidt, G, et al.. Anal Chem 2003;75:1895–904. Erratum in: Anal Chem 2003;75:4942. Johnstone, R [added]. Erratum in: Anal Chem 2006;78:4235. Mohammed A, Karim A [added]. https://doi.org/10.1021/ac0262560.Search in Google Scholar PubMed

31. Gillet, LC, Navarro, P, Tate, S, Röst, H, Selevsek, N, Reiter, L, et al.. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics 2012;11:O111.016717. https://doi.org/10.1074/mcp.O111.016717.Search in Google Scholar PubMed PubMed Central

32. Ow, SY, Cardona, T, Taton, A, Magnuson, A, Lindblad, P, Stensjö, K, et al.. Quantitative shotgun proteomics of enriched heterocysts from Nostoc sp. PCC 7120 using 8-plex isobaric peptide tags. J Proteome Res 2008;7:1615–28. https://doi.org/10.1021/pr700604v.Search in Google Scholar PubMed

33. Li, J, Van Vranken, JG, Vaites, LP, Schweppe, DK, Huttlin, EL, Etienne, C, et al.. TMTpro reagents: a set of isobaric labeling mass tags enables simultaneous proteome-wide measurements across 16 samples. Nat Methods 2020;17:399–404. https://doi.org/10.1038/s41592-020-0781-4.Search in Google Scholar PubMed PubMed Central

34. Ludwig, C, Gillet, L, Rosenberger, G, Amon, S, Collins, BC, Aebersold, R. Data-independent acquisition-based SWATH-MS for quantitative proteomics: a tutorial. Mol Syst Biol 2018;14:e8126. https://doi.org/10.15252/msb.20178126.Search in Google Scholar PubMed PubMed Central

35. Erickson, BK, Mintseris, J, Schweppe, DK, Navarrete-Perea, J, Erickson, AR, Nusinow, DP, et al.. Active instrument engagement combined with a real-time database search for improved performance of sample multiplexing workflows. J Proteome Res 2019;18:1299–306. https://doi.org/10.1021/acs.jproteome.8b00899.Search in Google Scholar PubMed PubMed Central

36. Schweppe, DK, Eng, JK, Yu, Q, Bailey, D, Rad, R, Navarrete-Perea, J, et al.. Full-featured, real-time database searching platform enables fast and accurate multiplexed quantitative proteomics. J Proteome Res 2020;19:2026–34. https://doi.org/10.1021/acs.jproteome.9b00860.Search in Google Scholar PubMed PubMed Central

37. Wakabayashi, I, Yanagida, M, Araki, Y. Associations of cardiovascular risk with circulating peptides related to hypertensive disorders of pregnancy. Hypertens Res 2021, in press. https://doi.org/10.1038/s41440-021-00747-6 Search in Google Scholar PubMed

38. Ker, JA, Soma-Pillay, P. NT-proBNP: when is it useful in obstetric medicine? Obstet Med 2018;11:3–5. https://doi.org/10.1177/1753495x17736717.Search in Google Scholar PubMed PubMed Central

39. Phipps, EA, Thadhani, R, Benzing, T, Karumanchi, SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 2019;15:275–89. Erratum in: Nat Rev Nephrol. 2019;15:386. https://doi.org/10.1038/s41581-019-0119-6.Search in Google Scholar PubMed PubMed Central

Received: 2021-06-18
Accepted: 2021-09-29
Published Online: 2021-10-19
Published in Print: 2022-01-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. EU health policy is on the brink of a spectacular own-goal that will harm patients and hamper innovation
  4. Theranos revisited: the trial and lessons learned
  5. Reviews
  6. Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT)
  7. High-sensitivity cardiac troponins in pediatric population
  8. Opinion Papers
  9. Implementation of the new EU IVD regulation – urgent initiatives are needed to avert impending crisis
  10. Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification
  11. General Clinical Chemistry and Laboratory Medicine
  12. Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module
  13. Instability of corticotropin during long-term storage – myth or reality?
  14. External quality assessment of serum indices: Spanish SEQC-ML program
  15. Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples
  16. Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum
  17. Hematology and Coagulation
  18. The development of autoverification system of lymphocyte subset assays on the flow cytometry platform
  19. Cancer Diagnostics
  20. Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients
  21. Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients
  22. Cardiovascular Diseases
  23. Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention
  24. Diabetes
  25. Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting
  26. Infectious Diseases
  27. Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value
  28. Acknowledgment
  29. Acknowledgment
  30. Letters to the Editors
  31. Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis
  32. Measuring accuracy of the neutralizing activity of COVID-19 convalescent plasma
  33. Evaluation of reference intervals for classical and alternative pathway functional complement assays
  34. Reference values for plasma neurofilament light chain in healthy Chinese children
  35. Cerebrospinal fluid neurogranin in Alzheimer’s disease studies: are immunoassay results interchangeable?
  36. Pepsin pretreatment corrects underestimation of 25-hydroxyvitamin D measurement by an automated immunoassay in subjects with high vitamin D binding protein levels
  37. A conspicuous reduced plasma creatinine: the first presenting sign of Waldenstrom macroglobulinemia
  38. Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800
https://doi.org/10.1515/cclm-2021-0713
Keywords for this article
disease biomarker; hypertensive disorders of pregnancy; peptidomics; quantitative proteomics

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. EU health policy is on the brink of a spectacular own-goal that will harm patients and hamper innovation
  4. Theranos revisited: the trial and lessons learned
  5. Reviews
  6. Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT)
  7. High-sensitivity cardiac troponins in pediatric population
  8. Opinion Papers
  9. Implementation of the new EU IVD regulation – urgent initiatives are needed to avert impending crisis
  10. Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification
  11. General Clinical Chemistry and Laboratory Medicine
  12. Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module
  13. Instability of corticotropin during long-term storage – myth or reality?
  14. External quality assessment of serum indices: Spanish SEQC-ML program
  15. Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples
  16. Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum
  17. Hematology and Coagulation
  18. The development of autoverification system of lymphocyte subset assays on the flow cytometry platform
  19. Cancer Diagnostics
  20. Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients
  21. Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients
  22. Cardiovascular Diseases
  23. Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention
  24. Diabetes
  25. Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting
  26. Infectious Diseases
  27. Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value
  28. Acknowledgment
  29. Acknowledgment
  30. Letters to the Editors
  31. Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis
  32. Measuring accuracy of the neutralizing activity of COVID-19 convalescent plasma
  33. Evaluation of reference intervals for classical and alternative pathway functional complement assays
  34. Reference values for plasma neurofilament light chain in healthy Chinese children
  35. Cerebrospinal fluid neurogranin in Alzheimer’s disease studies: are immunoassay results interchangeable?
  36. Pepsin pretreatment corrects underestimation of 25-hydroxyvitamin D measurement by an automated immunoassay in subjects with high vitamin D binding protein levels
  37. A conspicuous reduced plasma creatinine: the first presenting sign of Waldenstrom macroglobulinemia
  38. Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800
Stay updated on our offers and services
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 29.5.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2021-0713/html
Scroll to top button