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Published on: August 7, 2017
A Phase 1 Prognostic Trial for Predicting Paediatric Allergy Using the Placenta at Birth
Vicki L Clifton1, Zarqa Saif1, Ana Patricia Balbon2,3
1Mater Research Institute, The University of Queensland, Brisbane, Australia.
Insights
Placental gene expression can help predict childhood allergies. Specific glucocorticoid-regulated genes show promise in identifying children unlikely to develop allergies, aiding early intervention.
Area of Science:
- Reproductive biology and immunology
- Pediatric allergy research
- Genomic medicine
Background:
- Allergy is a common childhood non-communicable disease, necessitating early risk identification for intervention.
- Allergic disease origins are linked to early developmental events, including prenatal and early childhood exposures.
- Previous research identified associations between placental glucocorticoid-regulated genes and child allergy.
Purpose of the Study:
- To investigate the potential of using placental glucocorticoid-regulated mRNA profiles to predict childhood allergy risk.
- To determine if placental gene expression can serve as a biomarker for allergic susceptibility in children.
Main Methods:
- Analysis of placental samples from two Australian populations (South Australia, n=105; Victoria, n=261).
- Quantification of glucocorticoid-regulated genes using quantitative polymerase chain reaction (qPCR).
- Statistical modeling, including random forest analysis, performed using R (version 4.4.1).
Main Results:
- Top predictive genes identified: AFF1, ARID5B, IER3, ATF4, and SLC19A2.
- The best random forest model achieved an Area Under the Curve (AUC) of 0.664, indicating moderate predictive ability.
- Glucocorticoid-regulated genes demonstrated higher efficacy in identifying children who would not develop allergies.
Conclusions:
- Placental glucocorticoid-regulated genes hold significant predictive value for allergy risk, particularly for identifying non-allergic individuals.
- The study provides evidence of distinct transcriptional profiles in placentae of allergic versus nonallergic children.
- These findings support the placenta as a key site for understanding and potentially predicting early-onset allergic diseases.
Background:
Allergy is the most common and earliest onset non-communicable disease in children. The early identification of children who are at risk of allergy would allow early intervention to prevent the onset of the disease or reduce its impact. The origins of allergy are hypothesized to be derived from early developmental events which include prenatal events and early childhood exposures. We have previously identified that many placental glucocorticoid-regulated genes were also associated with child allergy.
Objective:
We have questioned if it is possible to predict which children are at risk of allergy based on their placental glucocorticoid-regulated mRNA profile.
Methods:
Placentae from two different populations located in South Australia (n = 105) and Victoria, Australia (n = 261) were included in the study. Glucocorticoid regulated genes were measured by qPCR. Statistical modelling was executed in R (version 4.4.1).
Results:
Evaluation of the importance of each gene in the model identified AFF1, ARID5B, IER3, ATF4 and SLC19A2 as the top five ranking genes. The best-performing random forest model achieved an AUC of 0.664, indicating moderate ability to distinguish between positive and negative allergic susceptibility. While our models demonstrate both measurable specificity and sensitivity, the glucocorticoid genes particularly excel at identifying children who will not develop an allergy.
Conclusion:
This study demonstrates that placental glucocorticoid-regulated genes possess significant predictive power, especially in identifying individuals unlikely to develop allergies. It offers further evidence that the placentae of nonallergic children and allergic children are transcriptionally distinct.
