Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence
Magnus Wickman,
Christian Lupinek,
Niklas Andersson,
Danielle Belgrave,
Anna Asarnoj,
Marta Benet,
Mariona Pinart,
Sandra Wieser,
Judith Garcia-Aymerich,
Alexandra Baar,
Göran Pershagen,
Angela Simpson,
Inger Kull,
Anna Bergström,
Erik Melén,
Carl Hamsten,
Josep M. Antó,
Jean Bousquet,
Adnan Custovic,
Rudolf Valenta,
Marianne van Hage
Affiliations
Magnus Wickman
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Christian Lupinek
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
Niklas Andersson
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Danielle Belgrave
Department of Paediatrics, Imperial College, London, UK
Anna Asarnoj
Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
Marta Benet
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
Mariona Pinart
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
Sandra Wieser
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
Judith Garcia-Aymerich
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
Alexandra Baar
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
Göran Pershagen
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Angela Simpson
Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
Inger Kull
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Anna Bergström
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Erik Melén
Institute of Environmental Medicine, Karolinska Institutet and Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
Carl Hamsten
Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
Josep M. Antó
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
Jean Bousquet
University Hospital, Montpellier; INSERM, VIMA: Ageing and chronic diseases, France
Adnan Custovic
Department of Paediatrics, Imperial College, London, UK
Rudolf Valenta
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
Marianne van Hage
Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
Background: Sensitization in early childhood may precede respiratory allergy in adolescence. Methods: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16 years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16 years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11 years (N = 248) and the outcome was studied at 11 years. Findings: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16 years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16 years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules. Interpretations: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16 years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.