bims-reprim Biomed News
on Reproductive immunology
Issue of 2020–11–29
two papers selected by
Iva Filipovic, Karolinska Institutet
  1. Human chorionic gonadotropin-mediated modulation of pregnancy-compatible peripheral blood natural killer cells in frozen embryo transfer cycles.
  2. Dysregulated immunity in SARS-CoV-2 infected pregnant women.
  1. Am J Reprod Immunol. 2020 Aug 15. e13324
    Human chorionic gonadotropin-mediated modulation of pregnancy-compatible peripheral blood natural killer cells in frozen embryo transfer cycles.
    Warren J Huber, May-Tal Sauerbrun-Cutler, Paula M Krueger, Geralyn Lambert-Messerlian, Surendra Sharma.
       PROBLEM: To evaluate pregnancy-compatible phenotypic and functional changes in peripheral blood natural killer (pNK) cells during frozen embryo transfer (FET) cycles.
    METHOD OF STUDY: Peripheral blood was collected from patients undergoing frozen embryo transfer cycles at three separate time points in the cycle. pNK cell phenotype was analyzed by flow cytometry. Impact of pregnancy status on pNK cell cytotoxicity was characterized by two methods: (1) a three-dimensional endovascular tube formation approach and (2) a NK cell-specific K562 cell kill assay.
    RESULTS: A total of 35 patients were enrolled, 15 with clinical pregnancies and 20 with negative serum β-hCG levels. Overall percentage of CD45+CD3-CD56+ pNK cell did not change during the FET cycle. Pregnancy resulted in an increase in CD45+CD3-CD56+ pNK cell population on the day of serum β-hCG. pNK cells from non-pregnant patients caused significant tube disruption when compared to pregnant patients. Addition of serum from pregnant women reduced the tube disruption by pNK cells from non-pregnant patients. pNK cells from pregnant patients showed significantly lower cytotoxicity toward K562 cells in serum-free conditions. The addition of pregnancy serum decreased non-pregnant pNK cell cytotoxicity. Pregnancy status had no impact on VEGF-A and VEGF-C serum levels. Recombinant hCG added to non-pregnant serum resulted in a significant reduction in non-pregnant pNK cell-mediated K562 cell kill.
    CONCLUSION: There was no difference in pNK cell populations based on timing of the FET cycle. However, pregnancy increased the percentage of CD45+CD3-CD56+ pNK cells. Additionally, pNK cells from pregnant women have reduced cytotoxicity and this is possibly mediated by hCG.
    Keywords:  frozen embryo transfer; human chorionic gonadotropin; human umbilical vascular endothelial cells; in vitro fertilization; peripheral blood natural killer cells
    DOI:  https://doi.org/10.1111/aji.13324
  2. medRxiv. 2020 Nov 16. pii: 2020.11.13.20231373. [Epub ahead of print]
    Dysregulated immunity in SARS-CoV-2 infected pregnant women.
    Morgan L Sherer, Jun Lei, Patrick Creisher, Minyoung Jang, Ramya Reddy, Kristin Voegtline, Sarah Olson, Kirsten Littlefield, Han-Sol Park, Rebecca L Ursin, Abhinaya Ganesan, Theresa Boyer, Diane M Brown, Samantha N Walch, Annukka A R Antar, Yukari C Manabe, Kimberly Jones-Beatty, William Christopher Golden, Andrew J Satin, Jeanne S Sheffield, Andrew Pekosz, Sabra L Klein, Irina Burd.
       Importance: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated.
    Objective: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women.
    Design: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood.
    Setting: Johns Hopkins Hospital (JHH).
    Participants: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study.
    Exposures: SARS-CoV-2.
    Main Outcomes and Measures: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression.
    Results: SARS-COV-2 positive pregnant women expressed more IL1β , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy.
    Conclusions and Relevance: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.
    DOI:  https://doi.org/10.1101/2020.11.13.20231373
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