Joining the Immunological Dots in Recurrent Miscarriage

Abstract

While raised cellular immunity mediated by T helper (Th) 1 type cells may be harmful for the developing embryo/foetus, it is likely that Th2 type immunity may be helpful. The role of natural killer (NK) cells is presently underestimated, although they are clearly important in angiogenesis and the coordinated invasion of the decidua by the trophoblast. Deficient T regulatory cell (Treg) function is evident in women with recurrent miscarriage particularly when this occurs in early pregnancy. The role of the pro-inflammatory Th17 cells is presently unclear. However, early evidence suggests that excessive Th17 activity may promote miscarriage and preterm delivery. This may relate to the ability of these cells to produce those cytokines that encourage Th1 and NK cell activity. As such recurrent miscarriage may be caused not only by chromosomal abnormalities, autoimmunity and uterine abnormalities but also by subclinical uterine infection and inflammation which by stimulating interleukin 6 favours Th17 development over Tregs. This review examines the role of these different cells in early pregnancy and suggests a schema that may join the dots of the immunological puzzle called pregnancy. Finally, suggestions are made as to how inappropriate immunity in recurrent miscarriage may be down-regulated using currently available therapies.

Association between functional polymorphisms of Foxp3 and Interleukin-21 genes with the occurrence of recurrent pregnancy loss in Gaza strip-Palestine

“…Dysregulated immunity was proposed as a potential mechanism underlying RPL 3,24 and that interindividual variation in the anti-inflammatory and proinflammatory cytokine levels may modify the risk of unexplained RPL. 7,25 In this regard, the success of pregnancy depends on maintaining a fine balance between Th1 and Th2 immunity. 26 This was reportedly characterized by a shift to Th2 (humoral) immunity, which involves augmentation in the production of Th2 cytokines accompanied by attenuation of Th1 cytokines synthesis.…”

“…6 Unregulated and excessive Th1 type immunity may be harmful to the fetus. 7 This is highlighted by a predominance of anti-inflammatory Th2 cytokines in normal pregnancy, and by the fact that poor pregnancy outcome is associated with heightened expression of proinflammatory Th1 cytokines.…”

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

“…The Journal of Immunology, 2016Immunology, , 196: 1132Immunology, -1145 P remature termination of pregnancy is one of the most important problems in reproductive medicine and obstetrics. Recurrent spontaneous abortions affect ∼1-2% of reproductive couples and often lead to childlessness, whereas preterm delivery occurs in 5-9% of successful pregnancies and is considered the major cause of perinatal morbidity and mortality (1)(2)(3)(4). During pregnancy the maternal immune system has to tolerate a semiallogeneic organism without immune rejection while maintaining the ability to combat infections.…”

“…During pregnancy the maternal immune system has to tolerate a semiallogeneic organism without immune rejection while maintaining the ability to combat infections. Dysfunction of the immune system during pregnancy either in terms of impaired tolerance induction or in terms of excessive inflammation can lead to severe pregnancy complications such as spontaneous abortion or preterm delivery (1,5).…”

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

“…O aborto espontâneo recorrente (AER) é caracterizado pela perda espontânea e consecutiva de três ou mais gestações até a 20ª semana de gravidez (Regan, 1998;Bansal, 2010), e acomete cerca de 1 a 2% das mulheres que estão na idade reprodutiva e pode chegar até 5% se levado em consideração as mulheres com duas perdas fetais consecutivas (Harger et al, 1983;Carrington, Sacks e Regan, 2005;Brenner, 2010). No entanto, a medida que as mulheres apresentam o evento do aborto, o risco de que a próxima gestação não seja bem sucedida aumenta de forma gradativa quando o aborto se repete (Barini e Al, 2000).…”