Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-ggqkh Total loading time: 0 Render date: 2025-04-24T20:05:21.692Z Has data issue: false hasContentIssue false

6 - Immunological factors and placentation: implications for pre-eclampsia

from Part I - Basic science

Published online by Cambridge University Press:  03 September 2009

By
Ashley Moffett  and
Susan E. Hiby
Edited by
Fiona Lyall  and
Michael Belfort
Fiona Lyall
Affiliation:
University of Glasgow
Michael Belfort
Affiliation:
University of Utah
Get access

Summary

Introduction

Pre-eclampsia only occurs during pregnancy, a physiological situation where allogeneic cells from two different individuals come into close contact. Furthermore, the development of the disease is dependent only on the presence of the placenta and not the fetus as the disease is frequently seen in complete hydatidiform mole where no fetus is present. Numerous epidemiological studies have given rise to the widely held view that immunological mechanisms probably contribute to the pathogenesis of this disease (and indeed other pregnancy disorders) (Dekker, 2002; Redman, 1991; Roberts and Lain, 2002; Walker, 2000). However, the molecular and biological mechanisms underlying this presumed maternal immune maladaptation remain unknown.

During pregnancy both the maternal and fetal immune systems would be expected to recognize the presence of each other's allogeneic cells. However, the acceptance of the fetal allograft by the mother is at variance with the rejection typically seen with organ grafts. If the transplant analogy is extended further it would be expected that the maternal immune reaction would exhibit both specificity and memory for particular paternal genes expressed by the placenta. In other words, is there a partner-specific effect which contributes to pregnancy success or failure? Therefore, in considering possible immunological factors in pre-eclampsia two broad questions arise: first, how does the maternal immune system normally allow a symbiotic relationship with the feto-placental unit and, second, can this symbiosis be altered in a partner-specific way in pre-eclampsia?

Type
Chapter
Information
Pre-eclampsia
Etiology and Clinical Practice
 , pp. 92 - 102
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Abdalla, H. I., Billett, A., Kan, A. K., et al. (1998). Obstetric outcome in 232 ovum donation pregnancies. Br. J. Obstet. Gynaecol., 105, 332–7.CrossRefGoogle ScholarPubMed
Adams, E. M. and Finlayson, A. (1961). Familial aspects of preeclampsia and hypertension in pregnancy. Lancet, 2, 1357.Google ScholarPubMed
Alderman, B. W., Sperling, R. S. and Daling, J. R. (1986). An epidemiological study of the immunogenetic aetiology of pre-eclampsia. Br. Med. J., 292, 372–4.CrossRefGoogle ScholarPubMed
Aldrich, C., Verp, M. S., Walker, M. A. and Ober, C. (2000). A null mutation in HLA-G is not associated with preeclampsia or intrauterine growth retardation. J. Reprod. Immunol., 47, 41–8.CrossRefGoogle ScholarPubMed
Basso, O., Christiansen, K. and Olsen, J. (2001). Higher risk of pre-eclampsia after change of partner. An effect of longer interpregnancy intervals?Epidemiology, 12, 624–9.CrossRefGoogle ScholarPubMed
Bermingham, J., Jenkins, D., McCarthy, T. and O'Brien, M. (2000). Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia. Biochem. Soc. Trans., 28, 215–19.CrossRefGoogle ScholarPubMed
Boks, D. E. and Braat, D. D. (1997). Pregnancy following oocyte donation. Ned. Tijdschr. Geneeskd., 141, 1641–3.Google ScholarPubMed
Carrington, M. and Norman, P. J. (2003). The KIR Gene Cluster, Vol. 2003, National Library of Medicine (US), National Center for Biotechnology Information, Bethesda, MD.Google Scholar
Cincotta, R. B. and Brennecke, S. P. (1998). Family history of pre-eclampsia as a predictor for pre-eclampsia in primigravidas. Int. J. Gynaecol. Obstet., 60, 23–7.CrossRefGoogle ScholarPubMed
Colonna, M., Spies, T., Strominger, J. L., et al. (1992). Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. Proc. Natl Acad. Sci. USA, 89, 7983–5.CrossRefGoogle ScholarPubMed
Colonna, M., Brooks, E. G., Falco, M., Ferrara, G. B. and Strominger, J. L. (1993). Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science, 260, 1121–4.CrossRefGoogle ScholarPubMed
Cook, M. A., Moss, P. A. and Briggs, D. C. (2003). The distribution of 13 killer-cell immunoglobulin-like receptor loci in UK blood donors from three ethnic groups. Eur. J. Immunogen., 30, 213–21.CrossRefGoogle ScholarPubMed
Cross, J. (2003). The genetics of pre-eclampsia: a feto-placental or maternal problem?Clin. Genet., 64, 96–103.CrossRefGoogle ScholarPubMed
Darmochwal-Kolarz, D., Rolinski, J., Leszczynska-Goarzelak, B. and Oleszczuk, J. (2002). The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients. Am. J. Reprod. Immunol., 48, 381–6.CrossRefGoogle ScholarPubMed
Dekker, G. (2002). The partner's role in the etiology of preeclampsia. J. Reprod. Immunol., 57, 203–15.CrossRefGoogle ScholarPubMed
Dekker, G. A., Robillard, P. Y. and Hulsey, T. C. (1998). Immune maladaptation in the etiology of preeclampsia: a review of corroborative epidemiologic studies. Obstet. Gynecol. Surv., 53, 377–82.CrossRefGoogle ScholarPubMed
Eskenazi, B., Fenster, L. and Sidney, S. (1991). A multivariate analysis of risk factors for preeclampsia. J. Am. Med. Ass., 266, 237–41.CrossRefGoogle ScholarPubMed
Esplin, M. S., Fausett, M. B., Fraser, A., et al. (2001). Paternal and maternal components of the predisposition to preeclampsia. N. Engl. J. Med., 344, 867–72.CrossRefGoogle ScholarPubMed
Fallon, P. G., Jolin, H. E., Smith, P., et al. (2002). IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9 and IL-13. Immunity, 17, 7–17.CrossRefGoogle ScholarPubMed
Feeney, J. G. and Scott, J. S. (1980). Pre-eclampsia and changed paternity. Eur. J. Obstet. Gynecol. Reprod. Biol., 11, 35–8.CrossRefGoogle ScholarPubMed
Gardner, L. and Moffett, A., (2003). Dendritic cells in the human decidua. Biol. Reprod., 69, 1438–46.CrossRef
Giebel, S., Locatelli, F., Lamparelli, T., et al. (2003). Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood, 102, 814–19.CrossRefGoogle ScholarPubMed
Gould, D. S. and Auchincloss, H. (1999). Direct and indirect recognition: the role of MHC antigens in graft rejection. Immunol. Today, 20, 77–82.CrossRefGoogle ScholarPubMed
Hiby, S. E., King, A., Sharkey, A. and Loke, Y. W. (1999). Molecular studies of trophoblast HLA-G: polymorphisms, isoforms, imprinting and expression in preimplantation embryo. Tissue Antigens, 53, 1–13.CrossRefGoogle ScholarPubMed
Hiby, S. E., Walker, J. J., O'Shaughnessy, K. M., Redman, C. W., Carrington, M., Trowsdale, J. and Moffett, A. (2004). Combination of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J. Exp. Med., 200, 957–65.CrossRefGoogle ScholarPubMed
Holmes, V. A., Wallace, J. M., Gilmore, W. S., McFaul, P. and Alexander, H. D. (2003). Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study. Cytokine, 21, 265–9.CrossRefGoogle ScholarPubMed
Hoy, J., Venn, A., Halliday, J., Kovacs, G. and Waalwyk, K. (1999). Perinatal and obstetric outcomes of donor insemination using cryopreserved semen in Victoria, Australia. Hum. Reprod., 14, 1760–4.CrossRefGoogle ScholarPubMed
Humphrey, K. E., Harrison, G. A., Cooper, D. W., Wilton, A. N., Brennecke, S. P. and Trudinger, B. J. (1995). HLA-G deletion polymorphism and pre-eclampsia/eclampsia. Br. J. Obstet. Gynaecol., 102, 707–10.CrossRefGoogle ScholarPubMed
Janeway, C. A. (1992). The immune system evolved to discriminate infectious nonself from non-infectious self. Immunol. Today, 13, 11–16.CrossRefGoogle Scholar
Karre, K. (2002). Immunology. A perfect mismatch. Science, 295, 2029–31.CrossRefGoogle ScholarPubMed
Karre, K., Ljunggren, H. G., Piontek, G. and Kiessling, R. (1986). Selective rejection of H-2 deficient lymphoma variants suggests alternative immune defence strategy. Nature, 319, 675–8.CrossRefGoogle ScholarPubMed
Kim, S., Liva, S. M., Dalal, M. A., Verity, M. A. and Voskuhl, R. R. (1999). Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology, 52, 1230–8.CrossRefGoogle ScholarPubMed
King, A., Boocock, C., Sharkey, A. M., et al. (1996). Evidence for the expression of HLA-C class I mRNA and protein by human first trimester trophoblast. J. Immunol., 156, 2068–76.Google Scholar
King, A., Allan, D. S., Bowen, M., et al. (2000a). HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. Eur. J. Immunol., 30, 1623–31.3.0.CO;2-M>CrossRefGoogle Scholar
King, A., Burrows, T. D., Hiby, S. E., et al. (2000b). Surface expression of HLA-C antigen by human extravillous trophoblast. Placenta, 21, 376–87.CrossRefGoogle Scholar
Klonoff-Cohen, H. S., Savitz, D. A., Cefalo, R. C. and McCann, M. F. (1989). An epidemiologic study of contraception and preeclampsia. J. Am. Med. Ass., 262, 3143–7.CrossRefGoogle ScholarPubMed
Krishnan, L., Guilbert, L. J., Wegmann, T. G., Belosevic, M. and Mosmann, T. R. (1996a). T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells. J. Immunol., 156, 653–62.Google Scholar
Krishnan, L., Guilbert, L. J., Russell, A. S., Wegmann, T. G., Mosmann, T. R. and Belosevic, M. (1996b). Pregnancy impairs resistance of C57BL/6 to Leishmania major infection and causes decreased antigen-specific IFN-gamma response and increased production of T helper 2 cytokines. J. Immunol., 156, 644–52.Google Scholar
Lanier, L. L. (1998). NK cell receptors. Ann. Rev. Immunol., 16, 359–93.CrossRefGoogle ScholarPubMed
Li, D. K. and Wi, S. (2000). Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy. Am. J. Epidemiol., 151, 57–62.CrossRefGoogle ScholarPubMed
Lie, R. T., Rasmussen, S., Brunborg, H., Gjessing, H. K., Lie-Nielsen, E. and Irgens, L. M. (1998). Fetal and maternal contributions to risk of pre-eclampsia: population based study. Br. Med. J., 316, 1343–7.CrossRefGoogle ScholarPubMed
Loke, Y. W. and King, A. (1995). Human Implantation: Cell Biology and Immunology. Cambridge: Cambridge University Press.Google Scholar
MacGillivray, I. (1958). Some observations on the incidence of preeclampsia. Obstet. Gynaecol. Br. Emp., 65, 536–9.CrossRefGoogle Scholar
Marti, J. J. and Herrmann, U. (1977). Immunogestosis: a new etiologic concept of ‘essential’ EPH gestosis, with special consideration of the primigravid patient. Am. J. Obstet. Gynecol., 128, 489–93.CrossRefGoogle ScholarPubMed
Martin, M. P., Nelson, G., Lee, J.-H., et al. (2002a). Susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles. J. Immunol., 169, 2818–22.CrossRefGoogle Scholar
Martin, M. P., Gao, X., Lee, J.-H., et al. (2002b). Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature Genet., 31, 429–34.CrossRefGoogle Scholar
Matzinger, P. (1994). Tolerance, danger, and the extended family. Ann. Rev. Immunol., 12, 991–1045.CrossRefGoogle ScholarPubMed
Mellor, A. L. and Munn, D. H. (2003). Tryptophan catabolism and regulation of adaptive immunity. J. Immunol., 170, 5809–13.CrossRefGoogle ScholarPubMed
Miyaura, H. and Iwata, M. (2002). Direct and indirect inhibition of Th1 development by progesterone and glucocorticoids. J. Immunol., 168, 1087–94.CrossRefGoogle ScholarPubMed
Moffett, A. and Loke, Y. W. (2004). The immunological paradox of pregnancy: a reappraisal. Placenta, 24, 1–8.CrossRef
Moffett, A. and Loke, Y. W. (2006). Immunology of placentation in eutherian mammals. Nat. Rev. Immunol., 6, 584–94.CrossRef
Moffett-King, A. (2002). Natural killer cells and pregnancy. Nature Rev. Immunol., 2, 656–63.CrossRefGoogle Scholar
Need, J. A., Bell, B., Meffin, E. and Jones, W. R. (1983). Pre-eclampsia in pregnancies from donor inseminations. J. Reprod. Immunol., 5, 329–38.CrossRefGoogle ScholarPubMed
O'Garra, A. (1998). Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity, 8, 275–83.CrossRefGoogle ScholarPubMed
Ostensen, M. (1999). Sex hormones and pregnancy in rheumatoid arthritis and systemic lupus erythematosus. Annals N.Y. Acad. Sci., 876, 131–43.CrossRefGoogle ScholarPubMed
Parham, P. and McQueen, K. L. (2003). Alloreactive killer cells: hindrance and help for haematopoietic transplants. Nature Rev. Immunol., 3, 108–22.CrossRefGoogle ScholarPubMed
Piccinni, M. P., Giudizi, M. G., Biagiotti, R., et al. (1995). Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J. Immunol., 155, 128–33.Google Scholar
Redman, C. W. (1991). Current topic: pre-eclampsia and the placenta. Placenta, 12, 301–8.CrossRefGoogle ScholarPubMed
Redman, C. W. and Sargent, I. L. (2003). Pre-eclampsia, the placenta and the maternal systemic inflammatory response – a review. Placenta, 24, S21–7.CrossRefGoogle ScholarPubMed
Rein, D. T., Schondorf, T., Gohring, U. J., et al. (2002). Cytokine expression in peripheral blood lymphocytes indicates a switch to T(HELPER) cells in patients with preeclampsia. J. Reprod. Immunol., 54, 133–42.CrossRefGoogle Scholar
Roberts, J. M. and Redman, C. W. (1993). Pre-eclampsia: more than pregnancy-induced hypertension. Lancet, 341, 1447–51.CrossRefGoogle ScholarPubMed
Roberts, J. M. and Lain, K. Y. (2002). Recent insights into the pathogenesis of pre-eclampsia. Placenta, 23, 359–72.CrossRefGoogle ScholarPubMed
Robillard, P.-Y., Hulsey, T. C., Perianin, J., Janky, E., Miri, E. H. and Papiernik, E. (1994). Association of pregnancy-induced hypertension with duration of sexual cohabitation before conception. Lancet, 344, 973–5.CrossRefGoogle ScholarPubMed
Robillard, P.-Y., Dekker, G. A. and Hulsey, T. C. (1998). Primipaternities in families: is the incidence of pregnancy-induced hypertensive disorders in multigravidas an anthropological marker of reproduction. Austr. N. Zeal. J. Obstet. Gynecol., 38, 284–7.CrossRefGoogle ScholarPubMed
Sacks, G. P., Redman, C. W. and Sargent, I. L. (2003). Monocytes are primed to produce the Th1 type cytokine IL-12 in normal human pregnancy: an intracellular flow cytometric analysis of peripheral blood mononuclear cells. Clin. Exp. Immunol., 131, 490–7.CrossRefGoogle ScholarPubMed
Saito, S., Umekage, H., Sakamoto, Y., et al. (1999). Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with preeclampsia. Am. J. Reprod. Immunol., 41, 297–306.CrossRefGoogle ScholarPubMed
Salha, O., Sharma, V., Dada, T., et al. (1999). The influence of donated gametes on the incidence of hypertensive disorders of pregnancy. Hum. Reprod., 14, 2268–73.CrossRefGoogle ScholarPubMed
Serhal, P. F. and Craft, I. L. (1989). Oocyte donation in 61 patients. Lancet, 1, 1185–7.CrossRefGoogle ScholarPubMed
Skjaerven, R., Wilcox, A. J. and Lie, R. T. (2002). The interval between pregnancies and the risk of preeclampsia. N. Engl. J. Med., 346, 33–8.CrossRefGoogle ScholarPubMed
Soderstrom-Anttila, V., Tiitinen, A., Foudila, T. and Hovatta, O. (1998). Obstetric and perinatal outcome after oocyte donation: comparison with in vitro fertilization pregnancies. Hum. Reprod., 13, 483–90.CrossRefGoogle ScholarPubMed
Sutherland, A., Cooper, D. W., Howie, P. W., Liston, W. A. and MacGillivray, I. (1981). The incidence of severe pre-eclampsia amongst mothers and mothers-in-law of pre-eclamptics and controls. Br. J. Obstet. Gynaecol., 88, 785–91.CrossRefGoogle ScholarPubMed
Suzuki, S., Kuwajima, T., Yoneyama, Y., Sawa, R. and Araki, T. (2002). Maternal peripheral T-helper 1-type and T-helper 2-type immunity in non preeclamptic twin pregnancies. Gynecol. Obstet. Invest., 53, 140–3.CrossRefGoogle Scholar
Svensson, L., Arvola, M., Sallstrom, M. A., Holmdahl, R. and Mattsson, R. (2001). The Th2 cytokines IL-4 and IL-10 are not crucial for the completion of allogeneic pregnancy in mice. J. Reprod. Immun., 51, 3–7.CrossRefGoogle Scholar
Treloar, S. A., Cooper, D. W., Brennecke, S. P., Grehan, M. M. and Martin, N. G. (2001). An Australian twin study of the genetic basis of preeclampsia and eclampsia. Am. J. Obstet. Gynecol., 184, 374–81.CrossRefGoogle ScholarPubMed
Trogstad, L. I., Eskild, A., Magnus, P., Samuelsen, S. O. and Nesheim, B. I. (2001). Changing paternity and time since last pregnancy; the impact on pre-eclampsia risk. A study of 547 238 women with and without previous pre-eclampsia. Int. J. Epidemiol., 30, 1317–22.CrossRefGoogle Scholar
Trowsdale, J. (2001). Genetic and functional relationships between MHC and NK receptor genes. Immunity, 15, 363–74.CrossRefGoogle ScholarPubMed
Trupin, L. S., Simon, L. P. and Eskenazi, B. (1996). Change in paternity: a risk factor for preeclampsia in multiparas. Epidemiology, 7, 240–4.CrossRefGoogle ScholarPubMed
Tubbergen, P., Lachmeijer, A. M., Althuisius, S. M., Vlak, M. E., Geijn, H. P. and Dekker, G. A. (1999). Change in paternity: a risk factor for pre-eclampsia in multiparous women?J. Reprod. Immunol., 45, 81–8.CrossRefGoogle ScholarPubMed
Valiante, N. M., Uhrberg, M., Shilling, H. G., et al. (1997). Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity, 7, 739–51.CrossRefGoogle ScholarPubMed
Verma, S., King, A. and Loke, Y. W. (1997). Expression of killer-cell inhibitory receptors on human uterine NK cells. Eur. J. Immunol., 27, 979–83.CrossRefGoogle Scholar
Vilches, C. and Parham, P. (2002). KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Ann. Rev. Immunol., 20, 217–51.CrossRefGoogle ScholarPubMed
Walker, J. J. (2000). Pre-eclampsia. Lancet, 356, 1260–5.CrossRefGoogle ScholarPubMed
Wang, J. X., Knottnerus, A.-M., Schuit, G., Norman, R. J., Chan, A. and Dekker, G. A. (2002). Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet, 359, 673–4.CrossRefGoogle ScholarPubMed
Witt, C. S., Whiteway, J. M., Warren, H. S., et al. (2002). Alleles of the KIR2DL4 receptor and their lack of association with pre-eclampsia. Eur. J. Immunol., 32, 18–29.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Yawata, M., Yawata, N., Abi-Rached, L. and Parham, P. (2002). Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Criti. Rev. Immunol., 22, 463–82.Google ScholarPubMed
Yoneyama, Y., Suzuki, S., Sawa, R., Yoneyama, K., Power, G. G. and Araki, T. (2002). Relation between adenosine and T-helper 1/T-helper 2 imbalance in women with preeclampsia. Obstet. Gynaecol., 99, 641–6.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×