Maternal antibodies primed to react to specific allergens can cross the placenta, passing on transiently allergic reactions to offspring, according to new preclinical research from a collaborative study by the Agency for Science, Technology and Research, KK Women’s and Children’s Hospital, and Duke-NUS Medical School in Singapore. The finding hints at why infants exhibit allergies so early in life and suggests possible targets for intervention.
SINGAPORE, 30 October 2020 – Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women’s and Children’s Hospital (KKH) and Duke-NUS Medical School in Singapore reported this week in the journal Science.
The study, which employed an animal model conducted according to the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines, shows that the key antibody responsible for triggering allergic reactions, immunoglobulin E (IgE), can cross the placenta and enter the foetus. When inside the foetus, the antibody binds to foetal mast cells, a type of immune cell that releases chemicals that trigger allergic reactions, from runny noses to asthma. After birth, newborn mice develop allergic reactions to the same type of allergen as their mothers at the time of first exposure – unlike adult mice, which require two exposures. Studies in the laboratory also showed that maternal IgE can bind to human foetal mast cells, indicating they might cross the placenta in humans in a similar way.
Dr Florent Ginhoux, Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), a senior co-author of the study, said, "There is currently a significant lack of knowledge on mast cells that are present early on in the developing foetus. Here, we discovered that foetal mast cells phenotypically mature through the course of pregnancy, and can be sensitised by IgE of maternal origin that cross the placental barrier. The study suggests that a highly allergic pregnant mother may potentially transfer her IgE to her baby that consequently develop allergic reactions when exposed to the first time to the allergen.”
“Allergies begin very early in life,” said Associate Professor Ashley St. John, an immunologist at Duke-NUS’ Emerging Infectious Diseases Programme and a senior co-author of the study. “Infants experience allergic responses closely linked with the mother’s allergic response in ways that cannot only be explained by genetics. This work emphasises one way that allergic responses can pass from the mother to the developing foetus, and shows how allergies can then persist after birth.”
As part of the study, following NACLAR guidelines, researchers exposed mice to ragweed pollen, a common allergen, prior to pregnancy. Mice that developed a sensitivity to the pollen had offspring that also showed an allergic reaction to ragweed. The sensitivity is allergen-specific; the offspring did not react to dust mites, another common allergen.
Notably, the transfer of sensitivity appears to fade with time. The newborn mice had allergic reactions when tested at four weeks, but less or none at six weeks.
The experimental studies were backed up with cellular tests and imaging, which showed maternal IgE bound to fetal mast cells, triggering the mast cells to release chemicals in reaction to an allergen, a process called degranulation.
This study further showed that the IgE transfer across the placenta requires the help of another protein, FcRN. Mice with FcRN knocked out lacked maternal IgE attached to their mast cells, and did not develop allergies after birth.
The study findings potentially open new intervention strategies to limit such transfer to minimise the occurrence of neonatal allergies. Currently, between 10 to 30 per cent of the world’s population are affected by allergies. This number is set to continue rising and a solution preventing allergies being passed from mother to child could potentially bring those numbers down over time.
“Our research has really exciting findings that may explain the high incidence of early onset atopic dermatitis (eczema) in children of mothers with clinically proven eczema, which parallel findings in our local birth cohort findings,” said Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine at KKH, Senior National Medical Research Council Clinician Scientist, and Vice Chair of Research with the Obstetrics and Gynaecology Academic Clinical Programme at the SingHealth Duke-NUS Academic Medical Centre. “From a clinical point of view, developing a further understanding in placental transfer of IgE, and the mechanism of foetal mast cell activation would be key to developing strategies to reduce the chance of eczema or other allergies from being transferred from mother to baby.”
The authors next aim to better understand the mechanism of IgE transfer through the placenta, how IgE binding to mast cells in foetal skin modulate their functions and how it could affect skin physiology after birth.
Reference: Msallam, R., Balla, J., Rathore, A.P.S., Kared, H., Malleret, B., et al. Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE. Science (2020).
About Duke-NUS Medical School
Duke-NUS is Singapore’s flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five signature research programmes and nine centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapore’s largest healthcare group. This strategic alliance has spawned 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.
For more information, please visit www.duke-nus.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis.
For ongoing news, visit www.a-star.edu.sg.
About KK Women’s and Children’s Hospital
KK Women's and Children’s Hospital (KKH) is Singapore’s largest tertiary referral centre for Obstetrics, Gynaecology, Paediatrics and Neonatology. Founded in 1858, the academic medical institution specialises in the management of high-risk conditions in women and children. A team of about 500 specialists adopt a compassionate, multi-disciplinary and holistic approach to treatment, and harness medical innovations and technology to deliver the best medical care possible.
As an Academic Medical Centre, KKH is a major teaching hospital for all three medical schools in Singapore, Duke-NUS Medical School, Yong Loo Lin School of Medicine and Lee Kong Chian School of Medicine. The 830-bed hospital also runs the largest specialist training programme for Obstetrics and Gynaecology and Paediatrics in the country. Both programmes are accredited by the Accreditation Council for Graduate Medical Education International (ACGME-I), and are highly rated for the high quality of clinical teaching and the commitment to translational research.
For more information, please visit www.kkh.com.sg.