Prevention of Recurrent Spontaneous Abortions by Leukocyte Transfusions

Taylor, C. G.; Faulk, W. Pagé; McIntyre, John A.

doi:10.1177/014107688507800804

Cited by 62 publications

(29 citation statements)

References 22 publications

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“…There is increasing evidence that some recurrent abortions in women might be preventable by immunization of the mother against paternal or third party alloantigens (Taylor & Faulk, 1981;Mowbray et ai, 1985). Ethical concerns limit the extent of studies on this subject in women but there now exist several models of pregnancy failure in mice and its correction by lymphocyte alloimmunization.…”

Section: Introductionmentioning

confidence: 99%

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

Chaouat¹,

Menu²,

Clark³

et al. 1990

Reproduction

470

219

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Summary. In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)\g=a\,\g=g\-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortionprone (CBA/J \m=x\DBA/2) and non-abortion prone (CBA/J \m=x\BALB/c,C3H \m=x\DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA \m=x\DBA/2, from 7 to 89% in CBA \m=x\ BALB/c, from 5 to 47% in C3H \m=x\ DBA/2. The effect was both gestational age-and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J \m=x\ DBA/2 mating combination, whereas the rates in CBA/J \m=x\ BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharride (LPS), which is known to lead to the release of TNF-\g=a\, had a similar effect, leading to gestational age-and dose-dependent enhancement of resorptions up to 100%.However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J \m=x\ DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.

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Section: Introductionmentioning

confidence: 99%

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

Chaouat¹,

Menu²,

Clark³

et al. 1990

Reproduction

470

219

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“…Treatment of unexplained recurrent spon taneous abortion (RSA) ranges from psycho therapy to aggressive immunotherapeutic in tervention [1], The practice of immunother apy remains controversial despite widespread use during the past 10 years [2][3][4], Immuniza tion of RSA patients with paternal [5] or third-party [6] leukocytes is an approach used for patients who fail to manifest adequate immune recognition of paternally inherited fetal antigens. This hyporeactivity is thought to be due to a lack of recognition of a group of cell surface molecules called trophoblast-lymphocvte cross-reactive (TLX) alloantigens [7]. '…”

Section: Introductionmentioning

confidence: 99%

Heparin and Pregnancy in Women with a History of Repeated Miscarriages

McIntyre

Taylor

Torry

et al. 1993

Pathophysiol Haemos Thromb

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Many patients who experience recurrent spontaneous abortions (RSA) have high titered antibodies to trophoblast antigens and/or negatively charged phospholipids. Pregnancy success has been documented in some of these patients subsequent to heparin treatment. The effect of heparin on in vitro assays used to detect antibodies to phospholipids and trophoblast antigens has been investigated. We have found that complement-mediated detection of antibodies to trophoblast and lymphocyte antigens is inhibited by absorption of sera with solid-phase heparin. The data show that such inhibition involves an inhibitor and a heparin-sensitive regulator of the inhibitor. Heparin inhibits binding of antiphospholipid antibodies to phospholipids in solid-phase ELISA. The mechanism for this inhibition appears to involve an interaction between heparin and antibody to phospholipid. These findings reveal novel heparin-mediated reactions that bridge immunological and hematological interactions. The extent of heparin modulation of these antibody reactivities should be clarified in future clinical trials involving heparin treatment for RSA.

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“…Immunotherapy using paternal lymphocytes and its beneficial effects on RPL have been discussed for decades. Through these debates, immunization with both paternal lymphocyte [57,58] and pooled allogeneic lymphocytes [59,60] have apparently improved the successful pregnancy rate; in one double-blind controlled study, a significant increase in successful pregnancy outcomes was reported among women who had been immunized with their husband's cells compared w ith women who had received autologous lymphocytes [58]. These early studies in the 1980s were subsequently confirmed by multicenter studies [61][62].…”

Section: Cd3mentioning

confidence: 99%

Effective Treatment for Recurrent Pregnancy Loss

Makino

2010

RIB

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Abstract:Understanding the etiology of recurrent pregnancy loss (RPL) has been increasing in importance in reproductive medicine, especially in societies with low birth rates. Since the cause of human miscarriage is often complicated and multifactorial, effective treatment for the successful maintenance of pregnancy requires the comprehensive clinical management of recurrent wastages. Immunology for the maintenance of pregnancy is a very attractive field; however, the role of immunology during human gestation cannot be confirmed in couples with a history of recurrent pregnancy loss unless other clinical causes of miscarriage are especially ruled out. Balanced chromosomal rearrangements have been found at an increased frequency in couples with recurrent pregnancy loss compared with the general population. The major anomalies are Robertosonian or reciprocal translocations, while most minor variants include pericentric inversion of chromosome 9. Both major and minor anomalies result in a spontaneous abortion rate of approximately 80-90%. Though the incidences of these chromosomal abnormalities vary in reported studies, a survey indicated an incidence of 9.8% (3.9% in male partners and 5.9% in female partners) among 1,639 couples with a history of recurrent pregnancy loss. Congenital uterine anomaly resulting in a suboptimal uterine environment may influence ovum implantation and early fetal development and may be a candidate in the etiology of reproductive wastage. A review on the relation between congenital uterine anomalies and the spontaneous abortion rate concluded that a precise diagnosis of uterine cavity deformity, especially arcuate uterus, is a key issue for determining the clinical prognosis during human gestation. After establishing diagnostic criteria for uterine cavity anomaly, 278 congenital uterine anomalies were detected in a series of 2,061 hysterosalpingographies (13.5%) performed in women with a history of recurrent pregnancy loss. Among these abnormalities, the incidences of spontaneous abortion were equally high among patients with arcuate uterus and those with partial septate uterus. A few studies on abortion mechanism in patients with congenital uterine anomalies have been reported. Histological findings using CD34-positive staining indicate the lack of a blood capillary system in both the uterine septum and the fundus muscle layer. The results of metroplastic surgery on congenital uterine anomaly are also controversial. Based on our fundamental findings of the maldistribution of uterine capillaries, we performed ideal metroplastic surgery in 173 women and significantly

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Prevention of Recurrent Spontaneous Abortions by Leukocyte Transfusions

Cited by 62 publications

References 22 publications

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy

Heparin and Pregnancy in Women with a History of Repeated Miscarriages

Effective Treatment for Recurrent Pregnancy Loss

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