Skip to main content

Advertisement

Log in

An evaluation of calprotectin as serum marker of preeclampsia: a systematic review of observational studies

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

Calprotectin is calcium-binding protein which can be found in the cytosol of neutrophils. Several studies have studied its levels in preeclamptic women; however, to date there is no consensus regarding its effectiveness in the field.

Purpose

To investigate whether serum calprotectin levels are elevated among preeclamptic women compared to healthy controls.

Materials and methods

We used Medline (1966–2015), Scopus (2004–2015), ClinicalTrials.gov (2008–2015), Cochrane Central Register of Controlled Trials CENTRAL (1999–2015) and Google Scholar (2004–2015) search engines in our primary search, together with reference lists from included studies.

Results

Seven studies were finally included in our systematic review which recruited 439 women (245 with preeclampsia and 194 healthy controls). Their methodological quality was relatively high as they reached a score that ranged between 6 and 7 according to the Ottawa–Newcastle classification. All included studies reported that the serum calprotectin levels were significantly elevated among preeclamptic patients (p < 0.05). One study suggested that patients with severe preeclampsia have significantly higher levels of calprotectin than patients with mild preeclampsia (p = 0.01). However, to date there is no evidence regarding specific cut-off values which would help screen women for preeclampsia, or even follow the course of the disease.

Conclusion

Current evidence suggests that serum calprotectin is significantly raised among women with preeclampsia during the third trimester. Future research is needed to reach firm conclusions regarding its use as a potential screening and surveillance marker during the pregnancy course of women at risk of developing preeclampsia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ronsmans C, Graham WJ. Maternal mortality: who, when, where, and why. Lancet. 2006;368:1189–200.

    Article  PubMed  Google Scholar 

  2. Thornton C, Dahlen H, Korda A, Hennessy A. The incidence of preeclampsia and eclampsia and associated maternal mortality in Australia from population-linked datasets: 2000–2008. Am J Obstet Gynecol. 2013;208(476):e1–5.

    PubMed  Google Scholar 

  3. Lisonkova S, Sabr Y, Mayer C, Young C, Skoll A, Joseph KS. Maternal morbidity associated with early-onset and late-onset preeclampsia. Obstet Gynecol. 2014;124:771–81.

    Article  PubMed  Google Scholar 

  4. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013;209:544 e1–12.

    Article  PubMed  Google Scholar 

  5. Jelin AC, Cheng YW, Shaffer BL, Kaimal AJ, Little SE, Caughey AB. Early-onset preeclampsia and neonatal outcomes. J Matern Fetal Neonatal Med. 2010;23:389–92.

    Article  PubMed  Google Scholar 

  6. Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv. 2011;66:497–506.

    Article  PubMed  Google Scholar 

  7. Naljayan MV, Karumanchi SA. New developments in the pathogenesis of preeclampsia. Adv Chronic Kidney Dis. 2013;20:265–70.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014;10:466–80.

    Article  PubMed  CAS  Google Scholar 

  9. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009;24:147–58.

    Article  Google Scholar 

  10. Verdonk K, Visser W, Steegers EA, Kappers M, Danser AH, van den Meiracker AH. New insights into the pathogenesis of pre-eclampsia: the role of angiogenesis-inhibiting factors. Ned Tijdschr Geneeskd. 2011;155:A2946.

    PubMed  Google Scholar 

  11. Zhou Y, McMaster M, Woo K, Janatpour M, Perry J, Karpanen T, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002;160:1405–23.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12:642–9.

    Article  PubMed  CAS  Google Scholar 

  13. Sahay AS, Sundrani DP, Joshi SR. Regional changes of placental vascularization in preeclampsia: a review. IUBMB Life 2015.

  14. Laresgoiti-Servitje E. A leading role for the immune system in the pathophysiology of preeclampsia. J Leukoc Biol. 2013;94:247–57.

    Article  PubMed  CAS  Google Scholar 

  15. Lok CA, Jebbink J, Nieuwland R, Faas MM, Boer K, Sturk A, et al. Leukocyte activation and circulating leukocyte-derived microparticles in preeclampsia. Am J Reprod Immunol. 2009;61:346–59.

    Article  PubMed  CAS  Google Scholar 

  16. Mellembakken JR, Aukrust P, Olafsen MK, Ueland T, Hestdal K, Videm V. Activation of leukocytes during the uteroplacental passage in preeclampsia. Hypertension. 2002;39:155–60.

    Article  PubMed  CAS  Google Scholar 

  17. Striz I, Trebichavs.ky I. Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiol Res. 2004;53:245–53.

    PubMed  CAS  Google Scholar 

  18. Nilsen T, Sunde K, Larsson A. A new turbidimetric immunoassay for serum calprotectin for fully automatized clinical analysers. J Inflamm (Lond). 2015;12:45.

    Article  Google Scholar 

  19. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wells GA, Shea B, O’Connel D, Peterson J, V W, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. www.ohri.ca/programs/clinical_epidemiology/oxford.asp, 2011.

  21. Liosi S, Briana DD, Gourgiotis D, Boutsikou M, Baka S, Marmarinos A, et al. Calprotectin in human cord blood: relation to perinatal parameters and restricted fetal growth. J Perinat Med. 2010;38:523–6.

    PubMed  Google Scholar 

  22. Staff AC, Braekke K, Johnsen GM, Karumanchi SA, Harsem NK. Circulating concentrations of soluble endoglin (CD105) in fetal and maternal serum and in amniotic fluid in preeclampsia. Am J Obstet Gynecol. 2007;197(176):e1–6.

    PubMed  Google Scholar 

  23. Akcum S, Zulfikaroglu E, Eserdag S, Ozcan U. Plasma Calprotectin Levels in Preeclamptic Normotensive Pregnant and Nonpregnant Women. 2014.

  24. Braekke K, Holthe MR, Harsem NK, Fagerhol MK, Staff AC. Calprotectin, a marker of inflammation, is elevated in the maternal but not in the fetal circulation in preeclampsia. Am J Obstet Gynecol. 2005;193:227–33.

    Article  PubMed  CAS  Google Scholar 

  25. Sugulle M, Kvehaugen AS, Braekke K, Harsem NK, Staff AC. Plasma calprotectin as inflammation marker in pregnancies complicated by diabetes mellitus and superimposed preeclampsia. Pregnancy Hypertens. 2011;1:137–42.

    PubMed  Google Scholar 

  26. Börekçi B, Aksoy H, Öztürk N, Kadanalı S. Correlation between calprotectin and oxidized LDL in preeclampsia. Turk J Med Sci. 2009;39:191–5.

    Google Scholar 

  27. Feng C, Tao Y, Shang T, Yu M. Calprotectin, RAGE and TNF-alpha in hypertensive disorders in pregnancy: expression and significance. Arch Gynecol Obstet. 2011;283:161–6.

    Article  PubMed  CAS  Google Scholar 

  28. Ramma W, Buhimschi IA, Zhao G, Dulay AT, Nayeri UA, Buhimschi CS, et al. The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia. Angiogenesis. 2012;15:333–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Zaid O, Abdel-Maksoud H, Elmagid A, Omnia M. Biochemical effect of pre eclampsia on serum calprotectin, ascorbic acid, Uric Acid and Calcium. Benha Veterinary Med J. 2014;27(2):217–24.

    Google Scholar 

  30. Holthe MR, Staff AC, Berge LN, Fagerhol MK, Lyberg T. Calprotectin plasma level is elevated in preeclampsia. Acta Obstet Gynecol Scand. 2005;84:151–4.

    Article  PubMed  Google Scholar 

  31. Ramma W, Buhimschi IA, Zhao G, Dulay AT, Nayeri UA, Buhimschi CS, et al. The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia. Angiogenesis. 2012;15:333–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Dale I, Brandtzaeg P, Fagerhol MK, Scott H. Distribution of a new myelomonocytic antigen (L1) in human peripheral blood leukocytes. Immunofluorescence and immunoperoxidase staining features in comparison with lysozyme and lactoferrin. Am J Clin Pathol. 1985;84:24–34.

    PubMed  CAS  Google Scholar 

  33. Brandtzaeg P, Dale I, Fagerhol MK. Distribution of a formalin-resistant myelomonocytic antigen (L1) in human tissues. I. Comparison with other leukocyte markers by paired immunofluorescence and immunoenzyme staining. Am J Clin Pathol. 1987;87:681–99.

    PubMed  CAS  Google Scholar 

  34. Nakashige TG, Zhang B, Krebs C, Nolan EM. Human calprotectin is an iron-sequestering host-defense protein. Nat Chem Biol 2015.

  35. Kerkhoff C, Klempt M, Sorg C. Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). Biochim Biophys Acta. 1998;1448:200–11.

    Article  PubMed  CAS  Google Scholar 

  36. Yui S, Nakatani Y, Mikami M. Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity. Biol Pharm Bull. 2003;26:753–60.

    Article  PubMed  CAS  Google Scholar 

  37. Espinoza J, Chaiworapongsa T, Romero R, Edwin S, Rathnasabapathy C, Gomez R, et al. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003;13:2–21.

    Article  PubMed  CAS  Google Scholar 

  38. Buimer M, Keijser R, Jebbink JM, Wehkamp D, van Kampen AH, Boer K, et al. Seven placental transcripts characterize HELLP-syndrome. Placenta. 2008;29:444–53.

    Article  PubMed  CAS  Google Scholar 

  39. Gallery ED, Campbell S, Arkell J, Nguyen M, Jackson CJ. Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals. Microvasc Res. 1999;57:340–6.

    Article  PubMed  CAS  Google Scholar 

  40. Isaksen B, Fagerhol MK. Calprotectin inhibits matrix metalloproteinases by sequestration of zinc. Mol Pathol. 2001;54:289–92.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Bian Z, Shixia C, Duan T. First-trimester maternal serum levels of sFLT1, PGF and ADMA predict preeclampsia. PLoS One. 2015;10:e0124684.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vasilios Pergialiotis.

Ethics declarations

Funding

The authors report they did not receive funding for the present paper.

Conflict of interest

None for all authors.

Additional information

Responsible Editor: John Di Battista.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 63 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pergialiotis, V., Prodromidou, A., Pappa, E. et al. An evaluation of calprotectin as serum marker of preeclampsia: a systematic review of observational studies. Inflamm. Res. 65, 95–102 (2016). https://doi.org/10.1007/s00011-015-0903-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-015-0903-0

Keywords

Navigation