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Published on: August 7, 2017
Longitudinal trajectories of allergen sensitization in children with different transcriptome profiles from COCOA
Eun Lee1, Jeong-Hyun Kim2, So-Yeon Lee3
1Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.
Insights
Four childhood allergen sensitization trajectories were identified. The "multiple sensitization" group showed increased allergy risks, potentially due to impaired barrier function, offering insights into allergic disease development.
Area of Science:
- Immunology
- Allergy Research
- Pediatric Health
Background:
- Allergen sensitization pathways are linked to various allergic diseases.
- Mechanisms connecting sensitization to disease phenotypes require further investigation.
Purpose of the Study:
- To identify distinct aeroallergen sensitization trajectories in children.
- To investigate the association between these trajectories and allergic disease phenotypes.
- To explore the underlying molecular mechanisms, including transcriptome and cytokine profiles.
Main Methods:
- Utilized skin prick test data from the COCOA birth cohort (n=549) at ages 3, 7, and 9.
- Classified sensitization to 13 aeroallergens (house dust mite, pollens, pets, mold) into trajectories using group-based multi-trajectory modeling.
- Performed blood transcriptome and cytokine analyses at age 7.
Main Results:
- Identified four trajectories: 'no sensitization' (42.8%), 'HDM only' (29.9%), 'pollen predominant' (6.0%), and 'multiple sensitization' (21.3%).
- 'HDM only' and 'pollen predominant' linked to allergic rhinitis and conjunctivitis.
- 'Multiple sensitization' associated with food allergy, atopic dermatitis, allergic rhinitis, and asthma, with elevated IL-2 and IL-5 levels. Transcriptome analysis revealed distinct molecular pathways for each trajectory, including B cell, T cell, and barrier function responses.
Conclusions:
- Four distinct childhood aeroallergen sensitization trajectories with unique transcriptome profiles were identified.
- "Multiple sensitization" trajectory is linked to increased allergic comorbidities.
- Potential mediation of allergic comorbidities by barrier dysfunction warrants further investigation.
Background:
Allergen sensitization trajectories are linked to diverse allergic disease phenotypes, but the underlying mechanisms remain unclear.
Methods:
The study used skin prick test data obtained from children in the COCOA birth cohort (n = 549) at 3, 7, and 9 years of age. Sensitization to 13 aeroallergens, categorized into four groups (house dust mite [HDM], pollens, pets, and mold), was assessed and classified into trajectories using group-based multi-trajectory modeling. Blood transcriptome and cytokine analyses at age 7 were also performed.
Results:
Four allergen sensitization trajectories were identified: "no sensitization" (42.8 %), "HDM only" (29.9 %), "pollen predominant" (6.0 %), and "multiple sensitization" (21.3 %). The "HDM only" and "pollen predominant" trajectories were associated with an increased risk of allergic rhinitis (AR) and allergic conjunctivitis. "Multiple sensitization" was associated with an increased risk of food allergy, atopic dermatitis, AR, and asthma during the first 9 years-of-age. IL-2 and IL-5 levels were elevated significantly in the "multiple sensitization" trajectory. Transcriptome analysis revealed that the "HDM only" trajectory was associated with B cell receptor responses, the "pollen predominant" trajectory was associated with MHC and T cell responses, and the "multiple sensitization" trajectory was associated with pathways related to barrier function, including IL-1 and tight junctions, while also sharing signaling pathways with both the "HDM only" and "pollen predominant" trajectories.
Conclusions:
Four aeroallergen sensitization trajectories with distinct transcriptome profile during childhood were detected. "Multiple sensitization" trajectory is associated with an increased risk of allergic comorbidities, potentially mediated through barrier dysfunction.
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