Document Type : Original Article(s)
Authors
1 Department of Pharmacology, Medical Physics, and Clinical Biochemistry, College of Medicine, Hawler Medical University, Erbil, Iraq
2 Department of Chemistry, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq
3 Department of Obstetrics and Gynecology, College of Medicine, Hawler Medical University, Erbil, Iraq
Abstract
Background: Preeclampsia (PE) is a multisystem disorder of unknown cause, leading to maternal and fetal morbidity and mortality. This study aimed to measure the inflammatory biomarkers alpha1-acid glycoprotein (α1-AGP) and protein-bound hexose (PBH) in the maternal circulation of women with PE and normotensive pregnant women, as well as in postnatal umbilical cord blood, to compare levels between groups and assess their association with PE.
Methods: A hospital-based case-control study was conducted from June 2024 to July 2025 at the Maternity Teaching Hospital in Erbil, Kurdistan Region, Iraq, including 104 preeclamptic and 99 normotensive pregnant women. Maternal and postnatal umbilical cord α1-AGP levels were measured using a BiotecSunlong ELISA kit (cut-off: 71.3 and 50.64 ng/mL, respectively), while PBH was measured using the orcinol colorimetric method (cut-off: 111 and 67.36 mg/dL, respectively).
Results: Maternal α1-AGP and PBH levels were significantly higher in preeclamptic women (P<0.001). In postnatal umbilical cord blood, α1-AGP was elevated in PE, while PBH showed no significant difference. Maternal and postnatal α1-AGP demonstrated a moderate positive correlation (ρ=0.522, P<0.001), whereas PBH showed a weak correlation (ρ=0.242, P=0.016). Receiver Operating Characteristic (ROC) analysis indicated excellent discrimination between groups, with an Area Under the Curve (AUC) of 1.00 for maternal α1-AGP and 0.964 for maternal PBH.
Conclusion: Maternal α1-AGP and PBH are significantly elevated in preeclampsia, with α1-AGP also higher in postnatal umbilical cord blood. The high AUC supports their relevance as biomarkers of maternal and postnatal inflammation in PE.
Highlights
Jian Hussein (Google Scholar)
Keywords
- Chappell LC, Brocklehurst P, Green ME, Hunter R, Hardy P, Juszczak E, et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet. 2019;394:1181-90. doi: 10.1016/s0140-6736(19)31963-4. PubMed PMID: 31472930; PubMed Central PMCID: PMC6892281.
- Shields LE, Goffman D, Caughey AB ACOG practice bulletin: Clinical management guidelines for obstetrician-gynecologists. Obstetrics and gynecology. 2020;135:e237-60.
- Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226:S844-s66. doi: 10.1016/j.ajog.2021.11.1356. PubMed PMID: 35177222; PubMed Central PMCID: PMC8988238.
- Sowmya S, Ramaiah A, Sunitha T, Nallari P, Jyothy A, Venkateshwari A. Evaluation of Interleukin-10 (G-1082A) Promoter Polymorphism in Preeclampsia. J Reprod Infertil. 2013;14:62-6. PubMed PMID: 23926566; PubMed Central PMCID: PMC3719316.
- Roy S, Kumar V, Kumar V, Behera BK. Acute Phase Proteins and their Potential Role as an Indicator for Fish Health and in Diagnosis of Fish Diseases. Protein Pept Lett. 2017;24:78-89. doi: 10.2174/0929866524666161121142221. PubMed PMID: 27903234.
- Aziz SB. High sensitivity C-reactive protein in preeclamptic (PE) women. Tikrit Med J. 2015;20:1-5.
- Cresswell JA, Alexander M, Chong MYC, Link HM, Pejchinovska M, Gazeley U, et al. Global and regional causes of maternal deaths 2009-20: a WHO systematic analysis. Lancet Glob Health. 2025;13:e626-e34. doi: 10.1016/s2214-109x(24)00560-6. PubMed PMID: 40064189; PubMed Central PMCID: PMC11946934.
- Robajac D, Masnikosa R, Miković Ž, Mandić V, Nedić O. Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction. Free Radic Res. 2015;49:984-9. doi: 10.3109/10715762.2015.1020798. PubMed PMID: 25812587.
- Kronborg CS, Allen J, Vittinghus E, Knudsen UB. Pre-symptomatic increase in urine-orosomucoid excretion in pre-eclamptic women. Acta Obstet Gynecol Scand. 2007;86:930-7. doi: 10.1080/00016340701371322. PubMed PMID: 17653877.
- Bottorff MB, Pieper JA, Boucher BA, Hoon TJ, Ramanathan J, Sibai BM. Lidocaine protein binding in preeclampsia. Eur J Clin Pharmacol. 1987;31:719-22. doi: 10.1007/bf00541302. PubMed PMID: 3556378.
- Kristensen K, Wide-Swensson D, Lindstrom V, Schmidt C, Grubb A, Strevens H. Serum amyloid a protein and C-reactive protein in normal pregnancy and preeclampsia. Gynecol Obstet Invest. 2009;67:275-80. doi: 10.1159/000214081. PubMed PMID: 19390201.
- Horowitz RN. Glycoprotein and other serum proteins of maternal serum. Am J Obstet Gynecol. 1969;105:216-9. doi: 10.1016/0002-9378(69)90061-1. PubMed PMID: 5810451.
- Liu XI, Green DJ, van den Anker JN, Rakhmanina NY, Ahmadzia HK, Momper JD, et al. Mechanistic Modeling of Placental Drug Transfer in Humans: How Do Differences in Maternal/Fetal Fraction of Unbound Drug and Placental Influx/Efflux Transfer Rates Affect Fetal Pharmacokinetics? Front Pediatr. 2021;9:723006. doi: 10.3389/fped.2021.723006. PubMed PMID: 34733804; PubMed Central PMCID: PMC8559552.
- Laurell CB. Orosomucoid and alpha 1-antitrypsin in maternal and fetal sera at parturition. Scand J Clin Lab Invest. 1968;21:136-8. doi: 10.3109/00365516809084275. PubMed PMID: 5706636.
- Rimington C. Seromucoid and the bound carbohydrate of the serum proteins. Biochem J. 1940;34:931-40. doi: 10.1042/bj0340931. PubMed PMID: 16747238; PubMed Central PMCID: PMC1265364.
- Winzler RJ. Glycoproteins. In: Putnam FW, editor. The Plasma Proteins. Vol 1. New York: Academic Press; 1960. p. 309-47. doi: 10.1016/B978-1-4832-2810-5.50016-5.
- Beardmore-Gray A, Seed PT, Fleminger J, Zwertbroek E, Bernardes T, Mol BW, et al. Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis. Am J Obstet Gynecol. 2022;227:218-30. doi: 10.1016/j.ajog.2022.04.034. PubMed PMID: 35487323.
- Ceciliani F, Lecchi C. The Immune Functions of α(1) Acid Glycoprotein. Curr Protein Pept Sci. 2019;20:505-24. doi: 10.2174/1389203720666190405101138. PubMed PMID: 30950347.
- Khamchun S, Thakaeng C, Na Lampang R. Serum alpha-1-antitrypsin level in the severity prognosis of systemic lupus erythematosus patients: Systematic exploration of novel biomarker. Biomedicine (Taipei). 2022;12:19-30. doi: 10.37796/2211-8039.1297. PubMed PMID: 35836976; PubMed Central PMCID: PMC9236717.
- Durmuş M, Uzunlar Ö, Çelik H, Çandar T. Does alpha-1-acid glycoprotein determine for infertility in polycystic ovary syndrome? Eur J Obstet Gynecol Reprod Biol. 2022;274:155-9. doi: 10.1016/j.ejogrb.2022.05.023. PubMed PMID: 35653904.
- Tarkun I, Arslan BC, Cantürk Z, Türemen E, Sahin T, Duman C. Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab. 2004;89:5592-6. doi: 10.1210/jc.2004-0751. PubMed PMID: 15531516.
- Chu CY, Singla VP, Wang HP, Sweet B, Lai LT. Plasma alpha 1-acid glycoprotein levels in pregnancy. Clin Chim Acta. 1981;112:235-40. doi: 10.1016/0009-8981(81)90382-x. PubMed PMID: 7016376.
- di Masi A, Trezza V, Leboffe L, Ascenzi P. Human plasma lipocalins and serum albumin: Plasma alternative carriers? J Control Release. 2016;228:191-205. doi: 10.1016/j.jconrel.2016.02.049. PubMed PMID: 26951925.
- Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens. 2014;4:97-104. doi: 10.1016/j.preghy.2014.02.001. PubMed PMID: 26104417.
- Saito S, Shiozaki A, Nakashima A, Sakai M, Sasaki Y. The role of the immune system in preeclampsia. Mol Aspects Med. 2007;28:192-209. doi: 10.1016/j.mam.2007.02.006. PubMed PMID: 17433431.
- Catarino C, Santos-Silva A, Belo L, Rocha-Pereira P, Rocha S, Patrício B, et al. Inflammatory disturbances in preeclampsia: relationship between maternal and umbilical cord blood. J Pregnancy. 2012;2012:684384. doi: 10.1155/2012/684384. PubMed PMID: 22685662; PubMed Central PMCID: PMC3366239.
- Bork K, Horstkorte R, Weidemann W. Increasing the sialylation of therapeutic glycoproteins: the potential of the sialic acid biosynthetic pathway. J Pharm Sci. 2009;98:3499-508. doi: 10.1002/jps.21684. PubMed PMID: 19199295.
- Thakkar V, Patel P, Prajapati N, Kaur R, Nandave M. Serum Levels of Glycoproteins are Elevated in Patients with Ovarian Cancer. Indian J Clin Biochem. 2014;29:345-50. doi: 10.1007/s12291-013-0380-6. PubMed PMID: 24966484; PubMed Central PMCID: PMC4062676.
- Dheebalakshmi N, Poonguzhali B. Serum glycoproteins in patients with severe depression compared with normal subjects. MedPulse Int J Biochem. 2018;7:56-9. doi: 10.26611/1002731.
- Dheebalakshmi N, Poonguzhali B. Serum glycoproteins in patients with severe depression compared with normal subjects. MedPulse Int J Biochem. 2018;7:56-9. doi: 10.26611/1002731.
- Staff AC, Braekke K, Harsem NK, Lyberg T, Holthe MR. Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2005;122:33-9. doi: 10.1016/j.ejogrb.2004.11.015. PubMed PMID: 15935542.
- Sun L, Shi M, Wang J, Han X, Wei J, Huang Z, et al. Overexpressed Trophoblast Glycoprotein Contributes to Preeclampsia Development by Inducing Abnormal Trophoblast Migration and Invasion Toward the Uterine Spiral Artery. Hypertension. 2024;81:1524-36. doi: 10.1161/hypertensionaha.124.22923. PubMed PMID: 38716674.
- DiPrisco B, Kumar A, Kalra B, Savjani GV, Michael Z, Farr O, et al. Glycosylated Fibronectin and Inhibin Are Lower and Anti-Müllerian Hormone Is Higher in Umbilical Cord Blood When Mothers Have Preeclampsia. Endocr Pract. 2020;26:318-27. doi: 10.4158/ep-2019-0448. PubMed PMID: 31859547.
- Tea I, Le Gall G, Küster A, Guignard N, Alexandre-Gouabau MC, Darmaun D, et al. 1H-NMR-based metabolic profiling of maternal and umbilical cord blood indicates altered materno-foetal nutrient exchange in preterm infants. PLoS One. 2012;7:e29947. doi: 10.1371/journal.pone.0029947. PubMed PMID: 22291897; PubMed Central PMCID: PMC3264558.