A review of immune cells and molecules in women with recurrent miscarriage

Abstract

Immunological rejection of the fetus due to recognition of paternal antigens by the maternal immune system, resulting in abnormal immune cells and cytokine production, is postulated to be one cause of unexplained pregnancy loss. Although there is evidence for this in rodents, there is less evidence in humans. This article focuses on studies in humans, and reviews the recent literature on the differences in immune cells and molecules in normal fertile women and women with recurrent miscarriage (RM). Although much of the evidence is contradictory, these studies do suggest differences in the expression of some immune cells and molecules in women with RM. Differences in the CD56+ population of cells are seen, and there is some evidence for an alteration in the ratio of Th1 and Th2 cytokines produced by peripheral blood monocytes (PBMCs) and clones of decidual CD4+ cells. There is also some evidence for differences in endometrial cytokine production, and in particular decreased production of pro-inflammatory cytokines such as interleukin-6. Possible reasons for the variations in data are discussed, and the importance of compartment (peripheral blood, endometrium or decidua) in which the cells and molecules are measured and the timing of the sampling, both with respect to the menstrual cycle and pregnancy (at the time or just after miscarriage) is emphasized.

Sterile inflammation and pregnancy complications: a review

“…Inversely, failure to mount a local inflammatory response in early or late gestation can also lead to adverse conditions, including miscarriages. Evidence shows that impaired inflammatory response is implicated in numerous female reproductive tract pathologies including menstrual disorders (Sales & Jabbour 2003), endometriosis-associated infertility (Gupta et al 2008), recurrent miscarriage (von Wolff et al 2000, Laird et al 2003, intrauterine growth restriction (Heyborne et al 1994), preeclampsia , Rinehart et al 1999) and preterm labor (Romero et al 2006. Infertility has an estimated global prevalence of 9% with >72 million infertile women worldwide (Boivin et al 2007), whereas preterm birth and preeclampsia, the two leading causes of perinatal mortality and morbidity, have an estimated prevalence of >11% (Blencowe et al 2013) and 3-5% (Ananth et al 2013 respectively.…”

Recurrent Miscarriage: A Review

“…The potential etiologies of RM can be divided into embryologically driven causes (mainly due to an abnormal embryonic karyotype) and maternally driven causes which affect the endometrium and/or placental development [14,15]. Thus, studies that focus on RM have examined factors related to age, genetics, antiphospholipid syndrome, thrombophilias, uterine anomalies, hormonal or metabolic disorders, infection, autoimmunity, sperm quality and life-style issues.…”

“…Considerable evidence has associated adverse immune responses with infertility problems, and proinflammation molecules have been reported to be involved in compromised endometrial receptivity and fetus implantation [14,61].…”

“…The most abundant immune cells in the uterine decidua around the time of implantation and early placental development are the uNK cells. Altered numbers of uNK cells have been associated with several human reproductive disorders, including RM [14,46,60].…”

“…However, although HLA-G shows little polymorphism, its mRNA undergoes alternative splicing to produce five main forms of the molecule. HLA-G is also expressed by human embryos, and measurements of sHLA-G in culture supernatants of early embryos obtained by IVF before transfer have shown that its presence appears to be essential for successful pregnancy outcome [14].…”