Congenital human cytomegalovirus infection is associated with decreased transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia.

Abstract

Background

Placentally-transferred maternal IgG protects against pathogens in early life, yet vertically-transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored.

Methods

We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a U.S-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive non-transmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year.

Results

Transplacental IgG transfer efficiency was decreased by 23% (95% CI 10-36%, p=0.0079) in cCMV-infected pairs and 75% of this effect (95% CI 28-174%, p=0.0085) was mediated by elevated maternal IgG levels (i.e., hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection.

Conclusions

Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/cid/ciab627

Publication Info

Semmes, Eleanor C, Shuk Hang Li, Jillian H Hurst, Zidanyue Yang, Donna Niedzwiecki, Genevieve G Fouda, Joanne Kurtzberg, Kyle M Walsh, et al. (2021). Congenital human cytomegalovirus infection is associated with decreased transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 10.1093/cid/ciab627 Retrieved from https://hdl.handle.net/10161/24709.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Hurst

Jillian Hurst

Assistant Professor in Pediatrics

Children's Health & Discovery Initiative:
The prenatal period, infancy, childhood, and adolescence, represent critical time periods of human development that include more developmental milestones than any other period of the lifespan. Conditions during these developmental windows – including biological, social, economic, health, and environmental factors – have a profound impact on lifelong health. The Children’s Health and Discovery Initiative (CHDI) was founded on the hypothesis that interventions early in life will improve population health across the lifespan. To this end, the overarching goal of the CHDI is to create a robust coalition of multidisciplinary investigators and a pipeline of infrastructure, data, and research projects focused on developing innovative approaches to identifying and modulating early life factors that impact lifelong health and well-being.

Intersections of the upper respiratory microbiome, environmental exposures, and childhood respiratory infections
Early life exposure to and colonization with microbes has a profound influence on the education of the immune system and susceptibility to viral and bacterial infections later in life. My research is focused on the influence of the upper respiratory microbiome on the development of recurrent respiratory infections, including acute otitis media (AOM), the leading cause of antibiotic prescriptions and healthcare consultations among children. Importantly, some children develop recurrent infections that are thought to be linked to dysbiosis of the nasopharyngeal microbiome. My overarching goals are to identify alterations in the upper respiratory microbiome associated with AOM and to elucidate host factors and exposures that predispose some children to the development of recurrent AOM episodes.

Yang

Lexie Zidanyue Yang

Biostatistician II

Education: Masters Degree, Biostatistics.  Duke University School of Medicine. 2018

Overview: Lexie graduated from the master’s program in biostatistics at Duke in 2018. Over the past five years, she has collaborated with doctors, residents, fellows, and medical students in the Department of Neurosurgery and Pharmacy. Additionally, she is currently working with a faculty member in Surgery to investigate the impact of environmental factors on certain diseases. Lexie has extensive experience in data management with large databases, including MarketScan, HCUP, and CMS Medicare. She has also worked with EHR data and has experience with data extraction from DEDUCE and CRDM. Her statistical interests include longitudinal analysis, mediation analysis, survival analysis and latent class analysis.

Educational Background
Master of Biostatistics
Duke University (Durham, NC, USA) 2016-2018

Bachelor of Science
Mathematics, Statistics
University of Wisconsin-Madison (Madison, WI, USA) 2013-2016
Shandong University (Shandong, China) 2011-2013

Niedzwiecki

Donna Niedzwiecki

Professor of Biostatistics & Bioinformatics

Primary interests include clinical trials design and the design and analysis of biomarker and imaging studies especially in the areas of GI cancer, lymphoma, melanoma, transplant and cancer immunotherapy.

Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics

Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine.   Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University.  The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program.  The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.

Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.

In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA.  She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.

Walsh

Kyle Walsh

Associate Professor in Neurosurgery

Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench science with statistical methods to study the neurobiology of glial senescence and gliomagenesis. This research interrogates human genomic and epigenomic profiles to identify both heritable and modifiable factors that contribute to neurologic and physical decline, applying these approaches to studying the shared neurobiology of cognition, glial senescence, and gliomagenesis. The lab has a long history studying telomere maintenance in pre-malignant cells and its role in the development of cancer, most notably glioblastoma.

Permar

Sallie Robey Permar

Adjunct Professor in the Department of Pathology

Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS to characterize the virus-specific immune responses and virus evolution in breast milk and develop a maternal vaccine regimen for protection against breast milk transmission of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific immune responses and virus evolution in vertically-transmitting and nontransmitting HIV-infected women, defining maternal immune responses that may protect against neonatal transmission of HIV. Importantly, Dr. Permar has established a nonhuman primate model of congenital CMV infection adn is using this model to establish the maternal immune responses that are necessary for protection against placental virus transmission. Finally, Dr. Permar is studying the impact and prevention of postnatal CMV transmission in preterm infants.


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