Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion

Hill, Joseph A.; Polgár, Katalin; Harlow, Bernard L.; Anderson, Deborah J.

doi:10.1016/s0002-9378(11)90589-4

Cited by 121 publications

(60 citation statements)

References 19 publications

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“…The Th1 response, especially TNF-a, IFN-g and IL-2, has been postulated to be detrimental to the survival of the conceptus [33][34][35]. When administered to pregnant mice, TNF-a, IFN-g and IL-2 cause miscarriage [36], which is then reversed by anti-TNF-a.…”

Section: T-helper 1 Versus T-helper 2 Responsementioning

confidence: 99%

Recurrent miscarriages: What is the role of cytokines?

Calleja‐Agius

Brincat

2008

Gynecological Endocrinology

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Recurrent miscarriage is defined as three or more consecutive miscarriages before 20 weeks of gestation. This condition is a frequent reproductive problem worldwide, affecting up to 1% of couples. Immune effector cell dysfunction has been implicated in the pathogenesis of early pregnancy loss. This dysfunction may involve defects in cytokines, growth factors and immunosuppressive factors at the maternofetal interface. This is a growing research field, especially the role of cytokines in recurrent miscarriage.

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Section: T-helper 1 Versus T-helper 2 Responsementioning

confidence: 99%

Recurrent miscarriages: What is the role of cytokines?

Calleja‐Agius

Brincat

2008

Gynecological Endocrinology

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“…Embryotoxic factors have been detected in the sera of patients with recurrent spontaneous abortions (RSA) or endometriosis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). About 24% (8,10) to 70% (2) of the sera of RSA patients and 0% (9) to 100% (7) of the endometriosis patients were found to be embryotoxic.…”

Section: Introductionmentioning

confidence: 99%

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Hart

Patton

Jacobson

et al. 2005

J Assist Reprod Genet

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Purpose : DNA-damaging factors have been reported in patients that failed to achieve pregnancy after assisted reproductive technologies (ART). The hypothesis was that increased circulating cell-free DNA released by damaged cells could predict unfavorable conditions leading to failed ART treatment. The objective was to compare the relative concentrations of cell-free DNA in the luteal phase sera of nonpregnant versus pregnant patients. Methods : Frozen-thawed sera (30 IVF cases) were obtained 1 week after embryo transfer. There were 16 pregnant and 14 nonpregnant cases and controls consisting of male sera (n = 8 cases). Modified isocratic capillary electrophoresis was performed and the images analyzed for cell-free DNA. Results : Circulating cell-free DNA were identified in the sera of all patients. The serum concentrations of high (12 kb) and low (1 kb) molecular weight cell-free DNA were similar for both nonpregnant and pregnant patients. Male control sera had higher cell-free DNA concentrations compared with females. Evaluation of sera from a control case showed no fluctuations in cell-free DNA concentrations throughout specific days of the menstrual cycle. Conclusions : The results do not support the use of the luteal phase cell-free DNA concentration as a marker for failed pregnancies. The equal concentrations of high and low molecular weight cell-free DNA and ladder band-like gel patterns suggested cell apoptosis as the source of DNA.

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“…Direct evidence for the shift of the maternal immune response from cell-mediated to humoralmediated has been observed in mice but not in humans. Nevertheless, it was recently shown that recurrent spontaneous abortion in humans is correlated with Th1 type immunity to the trophoblast [15][16][17]. CD4 + T helper cell clones can be divided in mice and humans into three cytokine-secreting distinct subsets defined as Th1, Th2 and Th0 [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy

Marzi

Viganò²,

Trabattoni

et al. 1996

Clinical and Experimental Immunology

569

380

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SUMMARYAntigen-and mitogen-stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age-and sex-matched non-pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3-month period, were undergoing a normal, nonpathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL-2 and interferon-gamma (IFN-°) accompanied by an increase in production of IL-4 and IL-10, was observed in normal pregnancy, with the lowest quantities of IL-2 and IFN-°and the highest quantities of IL-4 and IL-10 present in the third trimester of pregnancy. Statistically significant increased production of both IL-2 and IFN-°and reduced production of IL-10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

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Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion

Cited by 121 publications

References 19 publications

Recurrent miscarriages: What is the role of cytokines?

Recurrent miscarriages: What is the role of cytokines?

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy

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