Abnormal expression of the costimulatory molecule B7-H4 in placental chorionic villous and decidual basalis tissues of patients with preeclampsia and HELLP syndrome.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 8912860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0897 (Electronic) Linking ISSN: 10467408 NLM ISO Abbreviation: Am J Reprod Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Copenhagen : Wiley-Blackwell
      Original Publication: New York : Alan R. Liss, Inc., c1989-
    • Subject Terms:
      Chorionic Villi/*metabolism ; Decidua/*metabolism ; HELLP Syndrome/*metabolism ; Pre-Eclampsia/*metabolism ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/*metabolism; Adult ; Chorionic Villi/immunology ; Decidua/immunology ; Female ; HELLP Syndrome/immunology ; Humans ; Pre-Eclampsia/immunology ; Pregnancy ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/immunology
    • Abstract:
      Background: B7-H4, a checkpoint molecule of the B7 family, regulates a broad spectrum such as T-cell activation, cytokine secretion, tumour progression, and invasion capacities. Our previous data revealed that soluble B7-H4 (sB7-H4) blood serum levels are elevated in women at high risk for the hypertensive pregnancy disorder preeclampsia (PE) in the first trimester, as well as in patients with confirmed early/late-onset PE.
      Aim: We here aim to investigate the expression pattern of B7-H4 in placental tissues of PE and HELLP Syndrome versus control group.
      Methods: B7-H4 protein expression and localization were investigated by immunoblotting and co-immunohistochemistry in placental chorionic villous and decidual basalis tissues.
      Results: B7-H4 protein was prominently expressed at the cell membrane, in the cytoplasm of the syncytiotrophoblast (STB) and interstitial extravillous trophoblast (EVT). B7-H4 protein levels in placental chorionic villous tissue were significantly higher in women with early-onset/late-onset PE and HELLP, while it was decreased in decidual basalis tissues of early-onset PE and HELLP compared with controls.
      Conclusion: B7-H4 was inversely expressed in placental chorionic villous and decidual basalis tissues of PE and HELLP patients. The increase in B7-H4 in the STB in PE and HELLP may lead to excessive apical expression and release of soluble B7-H4 in the maternal circulation. In contrast, the decrease in B7-H4 in decidual basalis tissues could be related to the decrease in invasion ability of the EVT in PE. Thus, the current results strongly suggest that B7-H4 is involved in the pathogenesis of PE and HELLP.
      (© 2021 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)
    • References:
      Schumacher A, Sharkey DJ, Robertson SA, Zenclussen AC. Immune cells at the fetomaternal interface: how the microenvironment modulates immune cells to foster fetal development. J Immunol. 2018;201:325-334.
      Lokki AI, Heikkinen-Eloranta JK, Laivuori H. Immunogenetic conundrum of preeclampsia. Front Immunol. 2018;9:2630.
      Morita K, Tsuda S, Kobayashi E, et al. Analysis of TCR repertoire and PD-1 expression in decidual and peripheral CD8+ T cells reveals distinct immune mechanisms in miscarriage and preeclampsia. Front Immunol. 2020;11:1082.
      Colucci F. The immunological code of pregnancy. Science. 2019;365:862-863.
      Cudihy D, Lee R. The pathophysiology of pre-eclampsia: current clinical concepts. J Obstet Gynaecol. 2009;29:576-582.
      Zenclussen AC. Adaptive immune responses during pregnancy. Am J Reprod Immunol. 2013;69:291-303.
      Khalid F, Tonismae T. HELLP Syndrome. StatPearls [Internet]. 2020. https://www.ncbi.nlm.nih.gov/books/NBK560615/.
      Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785-799.
      Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170:1-7.
      Bellamy L, Casas J-P, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974.
      Veerbeek JH, Hermes W, Breimer AY, et al. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension. Hypertension. 2015;65:600-606.
      Xiong X, Demianczuk NN, Saunders LD, Wang FL, Fraser WD. Impact of preeclampsia and gestational hypertension on birth weight by gestational age. Am J Epidemiol. 2002;155:203-209.
      Staff AC. The two-stage placental model of preeclampsia: An update. J Reprod Immunol. 2019;34:1-10.
      Wojtowicz A, Zembala-Szczerba M, Babczyk D, et al. Early-and late-onset preeclampsia: a comprehensive cohort study of laboratory and clinical findings according to the New ISHHP criteria. Int J Hypertens. 2019;2019:4108271.
      Abildgaard U, Heimdal K. Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review. Eur J Obstet Gynecol Reprod Biol. 2013;166:117-123.
      Landi B, Tranquilli A. HELLP syndrome and placental inflammatory pathology. Minerva Ginecol. 2008;60:389-398.
      Toldi G, Vásárhelyi ZE, Rigó J Jr, et al. Prevalence of regulatory T-cell subtypes in preeclampsia. Am J Reprod Immunol. 2015;74:110-115.
      Kieffer TE, Scherjon SA, Faas MM, Prins JR. Lower activation of CD4+ memory T cells in preeclampsia compared to healthy pregnancies persists postpartum. J Reprod Immunol. 2019;136:102613.
      Stojanovska V, Zenclussen AC. Innate and adaptive immune responses in HELLP syndrome. Front Immunol. 2020;11:667.
      Sica GL, Choi I-H, Zhu G, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18:849-861.
      Prasad DV, Richards S, Mai XM, Dong C. B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity. 2003;18:863-873.
      Zang X, Kim J, Murphy K, Waitz R, Allison JP. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci USA. 2003;100:10388-10392.
      MacGregor HL, Ohashi PS. Molecular pathways: evaluating the potential for B7-H4 as an immunoregulatory target. Clin Cancer Res. 2017;23:2934-2941.
      Park GB, Song H, Kim YS, et al. Cell cycle arrest induced by engagement of B7-H4 on Epstein-Barr virus-positive B-cell lymphoma cell lines. Immunology. 2009;128:360-368.
      Suh W-K, Wang S, Duncan GS, et al. Generation and characterization of B7-H4/B7S1/B7x-deficient mice. Mol Cell Biol. 2006;26:6403-6411.
      Azuma T, Zhu G, Xu H, et al. Potential role of decoy B7-H4 in the pathogenesis of rheumatoid arthritis: a mouse model informed by clinical data. PLoS Medicine. 2009;6:e1000166.
      Mach P, Nolte-Boenigk L, Droste L, et al. Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia. Am J Reprod Immunol. 2018;80:e12988.
      Galazka K, Wicherek L, Pitynski K, et al. Changes in the subpopulation of CD25+ CD4+ and FOXP3+ regulatory T cells in decidua with respect to the progression of labor at term and the lack of analogical changes in the subpopulation of suppressive B7-H4+ macrophages-A preliminary report. Am J Reprod Immunol. 2009;61:136-146.
      Darmochwal-Kolarz D, Kludka-Sternik M, Kolarz B, et al. The expression of B7-H1 and B7-H4 co-stimulatory molecules on myeloid and plasmacytoid dendritic cells in pre-eclampsia and normal pregnancy. J Reprod Immunol. 2013;99:33-38.
      Göhner C, Plösch T, Faas MM. Immune-modulatory effects of syncytiotrophoblast extracellular vesicles in pregnancy and preeclampsia. Placenta. 2017;60:S41-S51.
      Knöfler M, Haider S, Saleh L, et al. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci. 2019;1-18.
      Hypertension G. Preeclampsia. ACOG Practice Bulletin No. 202. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2019;133:e1-e25.
      Brown MA, Magee LA, Kenny LC, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72:24-43.
      Stepan H, Herraiz I, Schlembach D, et al. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol. 2015;45:241.
      Xu Y, Plazyo O, Romero R, Hassan SS, Gomez-Lopez N. Isolation of leukocytes from the human maternal-fetal interface. J Vis Exp. 2015;99.e52863.
      Gellhaus A, Schmidt M, Dunk C, et al. Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associatedwith pre-eclampsia. Mol Hum Reprod. 2006;12(6):389-399.
      Lash G, Robson S, Bulmer J. Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta. 2010;31:S87-S92.
      O’Brien M, Dausset J, Carosella ED, Moreau P. Analysis of the role of HLA-G in preeclampsia. Hum Immunol. 2000;61(11):1126-1131.
      Schumacher A, Zenclussen AC. Effects of heme oxygenase-1 on innate and adaptive immune responses promoting pregnancy success and allograft tolerance. Front Pharmacol. 2015;5:288.
      Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180:499-506.
      Santner-Nanan B, Peek MJ, Khanam R, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183:7023-7030.
      Nguyen TA, Kahn DA, Loewendorf AI. Maternal-fetal rejection reactions are unconstrained in preeclamptic women. PLoS One. 2017;12:e0188250.
      Choi I-H, Zhu G, Sica GL, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol. 2003;171:4650-4654.
      Qiu F, Yuan C, Xu J, et al. Role of B7-H4 in the progression and prognosis of cervical inflammation to cancer after human papilloma virus infection. J Biomed Nanotechnol. 2019;15: 1043-1051.
      Mach P, Köninger A, Wicherek L, et al. Serum concentrations of soluble B7-H4 in early pregnancy are elevated in women with preterm premature rupture of fetal membranes. Am J Reprod Immunol. 2016;76:149-154.
      Young A, Thomson AJ, Ledingham M, et al. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod. 2002;66:445-449.
      Junus K, Centlow M, Wikström A-K, et al. Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease. Mol Hum Reprod. 2012;18(3):146-155.
      Steegers EA, Von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376:631-644.
    • Contributed Indexing:
      Keywords: B7-H4; HELLP; decidua basalis tissue; immune tolerance; placenta chorionic villi; preeclampsia
    • Accession Number:
      0 (V-Set Domain-Containing T-Cell Activation Inhibitor 1)
      0 (VTCN1 protein, human)
    • Publication Date:
      Date Created: 20210417 Date Completed: 20220125 Latest Revision: 20220125
    • Publication Date:
      20221213
    • Accession Number:
      10.1111/aji.13430
    • Accession Number:
      33864713