Sensitization to grass pollen allergen molecules in a birth cohort—natural Phl p 4 as an early indicator of grass pollen allergy

doi:10.1016/j.jaci.2020.01.006

Journal of Allergy and Clinical Immunology

Volume 145, Issue 4, April 2020, Pages 1174-1181.e6

https://doi.org/10.1016/j.jaci.2020.01.006 Get rights and content

Background

Grass pollen allergy is one of the most common allergies worldwide.

Objective

The aim of this study was to evaluate the usefulness of grass pollen allergen molecules for prediction of grass pollen allergy during childhood and up to adolescence.

Method

Questionnaire data and sera obtained from the study subjects at the ages of 4, 8, and 16 years from the population-based Barn/Children Allergy Milieu Stockholm Epidemiology birth cohort were used. Sera from 763 representative subjects with serum samples available at all 3 ages were analyzed for IgE reactivity to 8 Phleum pratense (Phl p) allergens (MeDALL [Mechanisms for the Development of Allergies] chip) and to timothy grass extract (ImmunoCAP). Allergic rhinitis to grass pollen (ARg) was defined as upper airway symptoms during grass pollen exposure.

Results

The prevalence of sensitization to any Phl p molecule was higher compared with that to timothy extract at all 3 ages: at the age of 4 years, 9.7% versus 6.8%; at the age of 8 years, 28.4% versus 15.3%; and at the age of 16 years, 37.1% versus 27.1%. General estimating equations analyses revealed that among children sensitized at the age of 4 years, the overall odds ratio (OR) of later ARg (up to 16 years) was increased only for IgE reactivity to Phl p 1 (OR = 4.9) and natural Phl p 4 (OR = 6.9). The likelihood of later symptoms increased with the number of allergen molecules; at the age of 4 years, 2 or more molecules predicted ARg to 78% and 3 or more molecules predicted ARg to 95%. A positive test result for timothy extract predicted ARg to 70%.

Conclusions

Natural Phl p 4 is a hitherto unrecognized early indicator of grass pollen allergy, in addition to Phl p 1. To identify grass pollen sensitization and predict later ARg, allergen molecules are of added value to timothy extract alone and may help clinicians improve prediction of grass pollen allergy.

Section snippets

The BAMSE cohort

We used data from the population-based BAMSE (Barn/Children, Allergy, Milieu, Stockholm, Epidemiology) birth cohort. The details of the study have been published previously.¹⁵ In brief, the cohort consists of 4089 children recruited shortly after birth, when baseline data were obtained; parental questionnaires on symptoms of allergy-related disorders were used repeatedly thereafter to obtain data until the children were 16 years old. The response rate at the latest follow up at the age of 16

Study population

Comparison of baseline characteristics between the study population (N = 763) and the original cohort of 4089 children revealed no major differences (Table E1, Online Repository).

IgE reactivity from childhood to adolescence

Sensitization to any Phl p molecule increased with increasing age (Fig 1). Among the molecules analyzed, the most prevalent sensitizing allergen molecule was Phl p 1, irrespective of age (Fig 1) (6.6% at the age of 4 years, 22.8% at the age of 8 years, and 31.2% at the age of 16 years), followed in order by Phl p 4

Discussion

Here we used a molecular allergen approach to detect grass pollen sensitization and to predict, early in life, symptoms up to adolescence in the population-based BAMSE birth cohort. The results revealed that grass pollen sensitization was significantly more prevalent when detected with allergen molecules than with timothy extract alone. At 4 years of age, the majority of the sensitized children were still asymptomatic and the probability of later symptoms increased with increasing number of

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: Supported by the Acta Oto-Laryngologica Foundation, the Stockholm County Council, the Swedish Asthma and Allergy Research Foundation, the Swedish Heart-Lung Foundation, the Swedish Research Council, and the European Commissionś Seventh Framework 29 Program MeDALL under grant agreement No. 261357.

: Disclosure of potential conflict of interest: M. Westman reports personal fees from ALK and Mylan outside the submitted work. C. Lupinek reports personal fees from Thermo Fisher Scientific outside the submitted work. I. Mittermann reports grants from the Austrian Science Fund outside the submitted work. E. Melén reports personal fees from Thermo Fisher Scientific and Novartis outside the submitted work. J. Bousquet reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Purina, Sanofi-Aventis, Takeda, Teva, and Uriach and shares from KYomed-Innov outside the submitted work. R. Valenta reports grants from the Austrian Science Fund and grants and personal fees from Viravaxx outside the submitted work. M. van Hage reports personal fees from Biomay AG, Hycor Biomedical LLC, Thermo Fisher Scientific, and ALK outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

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Rhinitis, sinusitis, and ocular allergySensitization to grass pollen allergen molecules in a birth cohort—natural Phl p 4 as an early indicator of grass pollen allergy

Background

Objective

Method

Results

Conclusions

Section snippets

The BAMSE cohort

Study population

IgE reactivity from childhood to adolescence

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

EBioMedicine

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Methods

J Allergy Clin Immunol

J Allergy Clin Immunol

Semin Immunol

J Allergy Clin Immunol

Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I

Allergy

Characteristics and immunobiology of grass pollen allergens

Int Arch Allergy Immunol

EAACI Molecular Allergology User's Guide

Pediatr Allergy Immunol

Multiple grass mixes as opposed to single grasses for allergen immunotherapy in allergic rhinitis

Clin Exp Allergy

Rhinitis, sinusitis, and ocular allergy
Sensitization to grass pollen allergen molecules in a birth cohort—natural Phl p 4 as an early indicator of grass pollen allergy