The investigation of serum nectin-4 levels in patients with early onset preeclampsia

Year 2023, Volume: 6 Issue: 6, 1193 - 1199, 29.10.2023

Züat Acar , Mehmet Obut , Zeynep Gedik Özköse , Sadun Sucu , Salim Sezer , Mevlüt Bucak , İsmail Dağ , Sezgi Güllü Erciyestepe , İsmail Özdemir

https://doi.org/10.32322/jhsm.1350858

Abstract

Aims: We aimed to investigate the level and predictive value of soluble nectin-4 in early onset preeclampsia (EOPE).
Methods: Forty-three patients with EOPE and 41 healthy normotensive pregnant women participated in this prospective case-control study. The groups were matched for gestational age and gravidity. Serum nectin-4 levels were compared between groups. The ROC curve was drawn to show the predictive value of nectin-4 for EOPE. Patients were followed up until the end of labor, and perinatal outcomes were recorded.
Results: The demographic characteristics of the two groups were similar. Serum nectin-4 level was significantly increased in EOPE cases compared to controls (226.46±119.6 ng/ml vs. 156.54±44.8 ng/ml, p=0.001). The ROC showed that at > 160.938, the sensitivity and specificity were 67.44% and 82.93%, respectively [AUC:0.822, (CI:0.724 - 0.897), and (p< 0.001)]. Significant inverse correlations were found between nectin-4 levels and poor obstetric outcomes.
Conclusion: Maternal serum nectin-4 levels were significantly higher in patients with EOPE compared with controls. Increased nectin-4 levels may contribute to the development of EOPE through possible oxidative, immunological, and inflammatory mechanisms adversely affecting trophoblastic cells.

Keywords

Early preeclampsia, nectin-4, preeclampsia, pregnancy

References

• Gestational Hypertension and Preeclampsia: ACOG practice bulletin, number 222. Obstet Gynecol. 2020;135(6):e237.
• Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013;209(6):544.e1-544.e12.
• Harmon QE, Huang L, Umbach DM, et al. Risk of fetal death with preeclampsia. Obstet Gynecol. 2015;125(3):628-635.
• Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094-1112.
• Redman CW, Sargent IL, Staff AC. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia? Placenta. 2014;35 Suppl:S20-25.
• Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv. 2011;66(8):497-506.
• Obut M, Oğlak SC. Expression of CD44 and IL-10 in normotensive and preeclamptic placental tissue. Ginekol Pol. 2020;91(6):334-341.
• Ito M, Nishizawa H, Tsutsumi M, et al. Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study. BMC Med Genet. 2018;19:166.
• Wang Y, Walsh SW. TNF alpha concentrations and mRNA expression are increased in preeclamptic placentas. J Reprod Immunol. 1996;32(2):157-169.
• Reymond N, Fabre S, Lecocq E, Adelaïde J, Dubreuil P, Lopez M. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem. 2001;276(46):43205-43215.
• Adu-Gyamfi EA, Czika A, Gorleku PN, et al. The involvement of cell adhesion molecules, tight junctions, and gap junctions in human placentation. Reprod Sci Thousand Oaks Calif. 2021;28(2):305-320.
• Fabre-Lafay S, Monville F, Garrido-Urbani S, et al. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer. 2007;7:73.
• Karabulut M, Gunaldi M, Alis H, et al. Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma. Clin Transl Oncol Off Publ Fed Span Oncol Soc Natl Cancer Inst Mex. 2016;18(2):160-171.
• Zhou Y, Damsky CH, Chiu K, Roberts JM, Fisher SJ. Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts. J Clin Invest. 1993;91(3):950-960.
• Oudejans CBM, van Dijk M, Oosterkamp M, Lachmeijer A, Blankenstein MA. Genetics of preeclampsia: paradigm shifts. Hum Genet. 2007;120(5):607-612.
• Esplin MS, Fausett MB, Fraser A, et al. Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med. 2001;344(12):867-872.
• Moffett-King A. Natural killer cells and pregnancy. Nat Rev Immunol. 2002;2(9):656-663.
• Meggyes M, Nagy DU, Szigeti B, et al. Investigation of mucosal-associated invariant T (MAIT) cells expressing immune checkpoint receptors (TIGIT and CD226) in early-onset preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2020;252:373-381.
• Hackmon R, Koifman A, Hyodo H, Glickman H, Sheiner E, Geraghty DE. Reduced third-trimester levels of soluble human leukocyte antigen G protein in severe preeclampsia. Am J Obstet Gynecol. 2007;197(3):255.e1-5.
• Steinborn A, Varkonyi T, Scharf A, Bahlmann F, Klee A, Sohn C. Early detection of decreased soluble HLA-G levels in the maternal circulation predicts the occurrence of preeclampsia and intrauterine growth retardation during further course of pregnancy. Am J Reprod Immunol NYN 1989. 2007;57(4):277-286.
• Goswami D, Tannetta DS, Magee LA, et al. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta. 2006;27(1):56-61.
• M-Rabet M, Cabaud O, Josselin E, et al. Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(4):769-776.
• Reches A, Ophir Y, Stein N, et al. Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity. J Immunother Cancer. 2020;8(1):e000266.
• Fu W, Ma Z, Lei C, Ding M, Hu S. TIGIT-Fc Promote Immune Tolerance at the Feto-maternal Interface [Internet]. bioRxiv. 2019:819243. doi: https://doi.org/10.1101/819243
• Yu X, Harden K, Gonzalez LC, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48-57.
• Rzymski T, Petry A, Kračun D, et al. The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress. Oncogene. 2012;31(31):3621-3634.
• Gomaa MF, Naguib AH, Swedan KH, Abdellatif SS. Serum tumor necrosis factor-α level and uterine artery Doppler indices at 11-13 weeks’ gestation for preeclampsia screening in low-risk pregnancies: a prospective observational study. J Reprod Immunol. 2015;109:31-35.
• Ma R, Gu Y, Groome LJ, Wang Y. ADAM17 regulates TNFα production by placental trophoblasts. Placenta. 2011;32(12):975-980.
• Siddharth S, Nayak A, Das S, et al. The soluble nectin-4 ecto-domain promotes breast cancer induced angiogenesis via endothelial Integrin-β4. Int J Biochem Cell Biol. 2018;102:151-160.
• Kim YN, Lee DS, Jeong DH, Sung MS, Kim KT. The relationship of the level of circulating antiangiogenic factors to the clinical manifestations of preeclampsia. Prenat Diagn. 2009;29(5):464-470.
• Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol. 2011;31(1):33-46.
• Hirashima C, Ohkuchi A, Matsubara S, et al. Alteration of serum soluble endoglin levels after the onset of preeclampsia is more pronounced in women with early-onset. Hypertens Res. 2008;31(8):1541-1548.
• Hu T, Wang G, Zhu Z, Huang Y, Gu H, Ni X. Increased ADAM10 expression in preeclamptic placentas is associated with decreased expression of hydrogen sulfide production enzymes. Placenta. 2015;36(8):947-950.
• Buchanan PC, Boylan KLM, Walcheck B, et al. Ectodomain shedding of the cell adhesion molecule nectin-4 in ovarian cancer is mediated by ADAM10 and ADAM17. J Biol Chem. 2017;292(15):6339-6351.
• Yoshizawa H, Nishizawa H, Ito M, et al. Increased levels of nectin-4 as a serological marker for pre-eclampsia. Fujita Med J. 2023;9(3):200-205.