Inflammatory biomarkers in the allergic march during childhood

Abstract

Introduction The prevalence of allergic diseases has rapidly increased during the last decades. The hygiene hypothesis postulates that this increase is due to environmental changes in the 20th century, causing an imbalanced, dysregulated or inappropriate T-cell response leading to excessive immune stimulation from T helper (Th) cells. The development of a stable immune balance early in life is essential to prevent allergic diseases and inflammation. Allergies and their symptoms appear in most children in an order related to their age. The allergic march refers to the typical sequence in which allergies often appear. The march usually begins with eczema (also known as atopic dermatitis (AD) and food allergy and will progress further to the development of rhinitis and then asthma. The allergic march appears to be caused when a local allergic response initiates systemic inflammation. This allergic inflammation is characterized by the recruitment and activation Th2 lymphocytes, eosinophils and basophils that contribute significantly to the allergic response. Long-term continuation results in chronic allergic inflammation such as seen in asthma. The natural history of the allergic march is still poorly understood. Better understanding of this process may lead to new targets to protect children from developing allergies and atopic diseases. Since inflammation plays a key role in this process, this thesis aims to give an overview of early inflammatory biomarkers which are possibly involved in the development and progression of the allergic march.

Methods A comprehensive PubMed search was conducted to identify all published studies specifically targeting inflammatory biomarkers in eczema, allergy, rhinitis and asthma detectible in saliva or serum of infants and preschool children. Results of the search were summarized per category inflammatory biomarker and analysed based on the results of individual trails. Useful results from the included studies are summarized in tables and the most frequently measured inflammatory biomarkers are discussed in more detail.

Results The search resulted in 42 publications that met the selection criteria for inclusion. All these studies measured inflammatory biomarkers in serum, no study was found measuring inflammatory biomarkers in saliva. The three classes of biomarkers that were most frequently measured were serum eosinophil cationic protein (sECP), chemokine (C-C motif) ligands (CCLs) and adhesion molecules.

Discussion The most important finding of our study was that there are very little publications on inflammatory biomarkers in saliva. Measurement of inflammatory biomarkers in saliva therefore seems to be very interesting to focus on in future research. sECP, CCLs and adhesion molecules were the most frequently documented inflammatory biomarkers in serum of infants and preschool children. Although most of them are elevated in allergic diseases and some even correlated to the severity of the diseases, their role in the development or as a predictive marker for the development of eczema, allergy, rhinitis and asthma remains unclear.