The Effects of IgG Purified from Women with SLE and Associated Pregnancy Loss on Rat Embryos in Culture

Matalon, Shay; Shoenfeld, Yehuda; Blank, Miri; Yacobi, S.; Blumenfeld, Zeev; Ornoy, Asher

doi:10.1034/j.1600-0897.2002.01084.x

Cited by 16 publications

(23 citation statements)

References 35 publications

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“…34,35 It is interesting to note that the current maternal proteomic study revealed elevated production of IGG in BN dams. Increases in maternal IL6 and TNFɑ levels have been shown in women with pre-eclampsia, pro-inflammatory markers that are also upregulated in BN dams.…”

Section: Ically-determined Immune Phenotypes With Non-pregnant Bn Ratsmentioning

confidence: 81%

“…Women with Th2-mediated inflammatory diseases such as systemic lupus erythematosus have higher frequency of pre-eclampsia and recurrent miscarriage in association with autoantibody production. 34,35 It is interesting to note that the current maternal proteomic study revealed elevated production of IGG in BN dams. Future assays will reveal whether BN dams produce antibodies that impair fetal growth or placental development.…”

Section: Ically-determined Immune Phenotypes With Non-pregnant Bn Ratsmentioning

confidence: 81%

“…35,36 Finally, BN rats are predisposed to develop allergen-induced asthma. 35,36 Finally, BN rats are predisposed to develop allergen-induced asthma.…”

Section: Ically-determined Immune Phenotypes With Non-pregnant Bn Ratsmentioning

confidence: 99%

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Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation

Sanchez

Molinaro

et al. 2019

American J Rep Immunol

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Problem:The Brown Norway (BN) rat is a model of T-helper 2 immune diseases, and also a model of pregnancy disorders that include placental insufficiency, fetal loss, and pre-eclampsia-like symptoms. The aim of this study was to investigate the plasma proteomic/cytokine profile of pregnant BN rats in comparison to that of the Lewis (LEW) rat strain.Method of study: Plasma proteomics differences were studied at day 13 of pregnancy in pooled plasma samples by differential in-gel electrophoresis, and protein identification was performed by mass spectrometry. Key protein findings and predicted cytokine differences were validated by ELISA using plasma from rats at various pregnancy stages. Proteomics data were used for ingenuity pathway analysis (IPA). Results:In-gel analysis revealed 74 proteins with differential expression between BN and LEW pregnant dams. ELISA studies confirmed increased maternal plasma levels of complement 4, prothrombin, and C-reactive protein in BN compared to LEW pregnancies. LEW pregnancies showed higher maternal plasma levels of transthyretin and haptoglobin than BN pregnancies. Ingenuity pathway analysis revealed that BN pregnancies are characterized by activation of pro-coagulant, reactive oxygen species, and immune-mediated chronic inflammation pathways, and suggested increased interleukin 6 and decreased transforming growth factor-β1 as potential upstream events. Plasma cytokine analysis revealed that pregnant BN dams have a switch from anti-to pro-inflammatory cytokines with the opposite switch observed in pregnant LEW dams.Conclusion: Brown Norway rats show a maternal pro-inflammatory response to pregnancy that likely contributes to the reproductive outcomes observed in this rat strain. K E Y W O R D Simmune cytokines, maternal plasma, pregnancy, proteomics, strain differences

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Section: Ically-determined Immune Phenotypes With Non-pregnant Bn Ratsmentioning

confidence: 81%

Section: Ically-determined Immune Phenotypes With Non-pregnant Bn Ratsmentioning

confidence: 81%

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Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation

Sanchez

Molinaro

et al. 2019

American J Rep Immunol

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“…At present, we have no explanation for these findings. However, emerging experimental evidence suggests that autoantibodies are implicated in pregnancy loss 10 through several potential pathogenetic mechanisms that involve a) reduction of embryo and yolk sac growth 34 as well as of trophoblast proliferation; 35 b) increase in the rate of trophoblast apoptosis; 35 adverse actions on molecules important for embryo and placental development such as laminin-1 36 and elastin. 37 Therefore, on the basis of these findings, it could be hypothesized that if the detection of ANA in a significant proportion of women with RPL can be interpreted as the expression of some derangement in the immune response or status in these subjects, then the detection of additional types of autoantibodies could represent the expression of a more marked disorder.…”

Section: Discussionmentioning

confidence: 99%

Antinuclear Autoantibodies in Women with Recurrent Pregnancy Loss

Ticconi

Rotondi

Veglia

et al. 2010

American J Rep Immunol

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“…The embryos were cultured in Dulbecco's Modified Eagle's Medium (DMEM)/F12 and 20% fetal calf serum (Ornoy et al, 2003a) in the presence of IgG and specific aPLA purified from SLE/APS patients with RPL, which were added to the culture medium in the same concentrations as in the original sera (Matalon et al, 2002;Ornoy et al, 2003b). At that stage, many of the embryonic organs have already been formed; therefore, it is expected that the main effects (if any at all) will be on embryonic growth and viability (Matalon et al, 2002). Reduced embryonic crown rump length (ECRL) and yolk sac diameter were measured in the embryos exposed to whole IgG obtained from patients with SLE/APS and RPL, in comparison to embryos that were exposed to IgG purified from healthy women or to embryos cultured in media without IgG.…”

Section: Rat Embryos and Human Placental Explants: Useful Culture Sysmentioning

confidence: 99%

Maternal autoimmune diseases and immunologically induced embryonic and fetoplacental damage

Ornoy

Chen

Silver

et al. 2004

Birth Defects Research

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BACKGROUND:Autoimmune diseases are a group of illnesses in which autoantibodies are produced against various organs, presenting with a variety of clinical symptoms. In this review, we discuss the different aspects of autoimmune diseases in pregnancy. We also describe experimental models that help to understand the etiology and pathogenesis of the effects of this maternal disease on the developing embryo, fetus and placenta. METHODS:The possible direct effects of sera or IgG obtained from women with systemic lupus erythematosus/antiphospholipid syndrome (SLE/APS) and recurrent pregnancy loss (RPL) were examined on cultured 10.5-and 11.5-day-old rat embryos and on cultured human placental explants, as compared to sera from healthy women or synthetic medium that were used as controls. In addition, we examined the effects of the sera obtained from these women after successful treatment that allowed the birth of normal infants. RESULTS: We observed increased embryonic death and anomalies in embryos cultured on sera and IgG from SLE/APS women. Similarly, when human placental explants were cultured on these sera, trophoblastic cell growth was reduced and apoptotic rate was increased. Successful treatment also reduced the damage caused by the sera from these women in the cultured embryos and placentas. CONCLUSIONS: Our results, and the cited studies, point to the important role of the placental damage in the etiology of RPL associated with SLE/APS. Animal models, both in vivo and in vitro, as well as cultured early human placental explants can be used successfully to understand some of the pathogenic aspects of SLE/APS and RPL.

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The Effects of IgG Purified from Women with SLE and Associated Pregnancy Loss on Rat Embryos in Culture

Abstract: Various antiphospholipid antibodies affect differently the growth and development of the embryo and the placenta.

Cited by 16 publications

References 35 publications

Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation

Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation

Antinuclear Autoantibodies in Women with Recurrent Pregnancy Loss

Maternal autoimmune diseases and immunologically induced embryonic and fetoplacental damage

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