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3. Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2

Author

Garcia-Flores, Valeria, Romero, Roberto, Xu, Yi, Theis, Kevin R., Arenas-Hernandez, Marcia, Miller, Derek, Peyvandipour, Azam, Bhatti, Gaurav, Galaz, Jose, Gershater, Meyer, Levenson, Dustyn, Pusod, Errile, Tao, Li, Kracht, David, Florova, Violetta, Leng, Yaozhu, Motomura, Kenichiro, Para, Robert, Faucett, Megan, Hsu, Chaur-Dong, Zhang, Gary, Tarca, Adi L., Pique-Regi, Roger, and Gomez-Lopez, Nardhy

Published
2022
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5. One-third of patients with eclampsia at term do not have an abnormal angiogenic profile.

Author

Chaiworapongsa, Tinnakorn, Romero, Roberto, Gotsch, Francesca, Gomez-Lopez, Nardhy, Suksai, Manaphat, Gallo, Dahiana M., Jung, Eunjung, Levenson, Dustyn, and Tarca, Adi L.

Subjects
PLACENTAL growth factor, BIOMARKERS, PREMATURE infants, CROSS-sectional method, DURATION of pregnancy, CELL receptors, PREECLAMPSIA, RISK assessment, COMPARATIVE studies, IMMUNOASSAY, PATHOLOGIC neovascularization, DESCRIPTIVE statistics, RESEARCH funding, ECLAMPSIA, DISEASE risk factors, DISEASE complications, BLOOD
Abstract

An abnormal angiogenic profile is present in about one-half of women with preeclampsia at term. Few studies examined the roles of angiogenic biomarkers in eclampsia. The aims of this study were to determine (1) whether the degree of an anti-angiogenic state, reflected by a low placental growth factor (PlGF) to soluble fms-like tyrosine kinase-1 (sFlt-1) ratio, in women with eclampsia differed from that of women with severe preeclampsia; and (2) the prevalence of women who had an abnormal angiogenic profile at the diagnoses of preterm and term eclampsia. A cross-sectional study was conducted to include women in the following groups: (1) uncomplicated pregnancy (n=40); (2) severe preeclampsia (n=50); and (3) eclampsia (n=35). Maternal serum concentrations of PlGF and sFlt-1 were determined by immunoassays. Women with preterm, but not term, eclampsia had a more severe anti-angiogenic state than those with severe preeclampsia (lower PlGF and PlGF/sFlt-1 ratio, each p<0.05). However, the difference diminished in magnitude with increasing gestational age (interaction, p=0.005). An abnormal angiogenic profile was present in 95% (19/20) of women with preterm eclampsia but in only 67% (10/15) of women with eclampsia at term. Angiogenic biomarkers can be used for risk assessment of preterm eclampsia. By contrast, a normal profile of angiogenic biomarkers cannot reliably exclude patients at risk for eclampsia at term. This observation has major clinical implications given that angiogenic biomarkers are frequently used in the triage area as a test to rule out preeclampsia. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

Author

Garcia-Flores, Valeria, primary, Romero, Roberto, additional, Xu, Yi, additional, Theis, Kevin, additional, Arenas-Hernandez, Marcia, additional, Miller, Derek, additional, Peyvandipour, Azam, additional, Galaz, Jose, additional, Levenson, Dustyn, additional, Bhatti, Gaurav, additional, Gershater, Meyer, additional, Pusod, Errile, additional, Kracht, David, additional, Florova, Violetta, additional, Leng, Yaozhu, additional, Tao, Li, additional, Faucett, Megan, additional, Para, Robert, additional, Hsu, Chaur-Dong, additional, Zhang, Gary, additional, Tarca, Adi, additional, Pique-Regi, Roger, additional, and Gomez-Lopez, Nardhy, additional

Published
2021
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8. Pregnancy-specific transcriptional changes upon endotoxin exposure in mice

Author

Motomura, Kenichiro, primary, Romero, Roberto, additional, Tarca, Adi L., additional, Galaz, Jose, additional, Bhatti, Gaurav, additional, Done, Bogdan, additional, Arenas-Hernandez, Marcia, additional, Levenson, Dustyn, additional, Slutsky, Rebecca, additional, Hsu, Chaur-Dong, additional, and Gomez-Lopez, Nardhy, additional

Published
2020
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10. Intra-Amniotic Infection with Ureaplasma parvum Causes Preterm Birth and Neonatal Mortality That Are Prevented by Treatment with Clarithromycin

Author

Motomura, Kenichiro, primary, Romero, Roberto, additional, Xu, Yi, additional, Theis, Kevin R., additional, Galaz, Jose, additional, Winters, Andrew D., additional, Slutsky, Rebecca, additional, Garcia-Flores, Valeria, additional, Zou, Chengrui, additional, Levenson, Dustyn, additional, Para, Robert, additional, Ahmad, Madison M., additional, Miller, Derek, additional, Hsu, Chaur-Dong, additional, and Gomez-Lopez, Nardhy, additional

Published
2020
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12. Microbial burden and inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes

Author

Theis, Kevin R., primary, Romero, Roberto, additional, Motomura, Kenichiro, additional, Galaz, Jose, additional, Winters, Andrew D., additional, Pacora, Percy, additional, Miller, Derek, additional, Slutsky, Rebecca, additional, Florova, Violetta, additional, Levenson, Dustyn, additional, Para, Robert, additional, Varrey, Aneesha, additional, Kacerovsky, Marian, additional, Hsu, Chaur-Dong, additional, and Gomez-Lopez, Nardhy, additional

Published
2020
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15. Intra-Amniotic Infection with Ureaplasma parvumCauses Preterm Birth and Neonatal Mortality That Are Prevented by Treatment with Clarithromycin

Author

Motomura, Kenichiro, Romero, Roberto, Xu, Yi, Theis, Kevin R., Galaz, Jose, Winters, Andrew D., Slutsky, Rebecca, Garcia-Flores, Valeria, Zou, Chengrui, Levenson, Dustyn, Para, Robert, Ahmad, Madison M., Miller, Derek, Hsu, Chaur-Dong, and Gomez-Lopez, Nardhy

Abstract

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Multiple etiologies are associated with preterm birth; however, 25% of preterm infants are born to a mother with intra-amniotic infection, most commonly due to invasion of the amniotic cavity by Ureaplasmaspecies. Much research has focused on establishing a link between Ureaplasmaspecies and adverse pregnancy/neonatal outcomes; however, little is known about the taxonomy of and host response against Ureaplasmaspecies. Here, we applied a multifaceted approach, including human samples, in vivomodels, and in vitromanipulations, to study the maternal-fetal immunobiology of Ureaplasmainfection during pregnancy. Furthermore, we investigated the use of clarithromycin as a treatment for this infection. Our research provides translational knowledge that bolsters scientific understanding of Ureaplasmaspecies as a cause of adverse pregnancy/neonatal outcomes and gives strong evidence for the use of clarithromycin as the recommended treatment for women intra-amniotically infected with Ureaplasmaspecies.

Published
2020
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16. Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice.

Author

Garcia-Flores V, Liu Z, Romero R, Pique-Regi R, Xu Y, Miller D, Levenson D, Galaz J, Winters AD, Farias-Jofre M, Panzer JJ, Theis KR, and Gomez-Lopez N

Abstract

Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Published
2024
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17. Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2.

Author

Garcia-Flores V, Romero R, Xu Y, Theis K, Arenas-Hernandez M, Miller D, Peyvandipour A, Galaz J, Levenson D, Bhatti G, Gershater M, Pusod E, Kracht D, Florova V, Leng Y, Tao L, Faucett M, Para R, Hsu CD, Zhang G, Tarca AL, Pique-Regi R, and Gomez-Lopez N

Abstract

Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal inflammatory responses in the circulation and at the maternal-fetal interface, the latter being governed by T cells and macrophages. SARS-CoV-2 infection during pregnancy was also associated with a cytokine response in the fetal circulation (i.e. umbilical cord blood) without compromising the cellular immune repertoire. Moreover, SARS-CoV-2 infection neither altered fetal cellular immune responses in the placenta nor induced elevated cord blood levels of IgM. Importantly, SARS-CoV-2 was not detected in the placental tissues, nor was the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and further emphasizes the rarity of placental infection.

Published
2021
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