The puzzle of immune phenotypes of childhood asthma

Abstract

Asthma represents the most common chronic childhood disease worldwide. Whereas preschool children present with wheezing triggered by different factors (multitrigger and viral wheeze), clinical asthma manifestation in school children has previously been classified as allergic and non-allergic asthma. For both, the underlying immunological mechanisms are not yet understood in depth in children. Treatment is still prescribed regardless of underlying mechanisms, and children are not always treated successfully. This review summarizes recent key findings on the complex mechanisms of the development and manifestation of childhood asthma. Whereas traditional classification of childhood asthma is primarily based on clinical symptoms like wheezing and atopy, novel approaches to specify asthma phenotypes are under way and face challenges such as including the stability of phenotypes over time and transition into adulthood. Epidemiological studies enclose more information on the patient’s disease history and environmental influences. Latest studies define endotypes based on molecular and cellular mechanisms, for example defining risk and protective single nucleotide polymorphisms (SNPs) and new immune phenotypes, showing promising results. Also, regulatory T cells and recently discovered T helper cell subtypes such as Th9 and Th17 cells were shown to be important for the development of asthma. Innate lymphoid cells (ILC) could play a critical role in asthma patients as they produce different cytokines associated with asthma. Epigenetic findings showed different acetylation and methylation patterns for children with allergic and non-allergic asthma. On a posttranscriptional level, miRNAs are regulating factors identified to differ between asthma patients and healthy controls and also indicate differences within asthma phenotypes. Metabolomics is another exciting chapter important for endotyping asthmatic children. Despite the development of new biomarkers and the discovery of new immunological molecules, the complex puzzle of childhood asthma is still far from being completed. Addressing the current challenges of distinct clinical asthma and wheeze phenotypes, including their stability and underlying endotypes, involves addressing the interplay of innate and adaptive immune regulatory mechanisms in large, interdisciplinary cohorts.

A strategy for high‐dimensional multivariable analysis classifies childhood asthma phenotypes from genetic, immunological, and environmental factors

“…However, clinical practice and also molecular studies still divide children into two main phenotypes, namely allergic and nonallergic asthma . Attempts were made to disentangle distinct underlying pathophysiological mechanisms, but were hampered by the complex nature of the disease . While singular targets were identified, one could not consistently pinpoint a reliable pattern of relevant pathways critical for asthma phenotype differentiation and in the long‐term potentially patient‐tailored treatment of the disease.…”

Sustained Inhibition of the IL4/IL13 Receptor Complex during Allergen Specific Immunotherapy

“…As mice from the positive control group were severely sicker than mice from the AIT-groups it is clear that the number of FoxP3 + cells alone does not provide information about the immunological tolerance of an organism. Also studies in humans observed increased numbers of Tregs in asthmatic patients (Landgraf-Rauf et al, 2016). One could speculate whether rather the quality and not the quantity of regulatory T cells is decisive for tolerance induction.…”

Markers of Transient and Persistent Bronchial Obstruction Syndrome Phenotype in Children

“…Результаты исследования свидетельствуют, что у детей с персистирующим фенотипом бронхиальной обструкции вне зависимости от пола и возраста статистически значимо повышаются концентрации как провоспалительных (IL-6, IL-8), так и противовоспалительных цитокинов (IL-4). Клинические данные свидетельствуют о значимости Th2цитокина IL-4 в поддержании воспаления и формировании бронхиальной гиперреактивности [6][7][8][9][10]. Вместе с тем в ряде исследований показано, что повышение уровней провоспалительных цитокинов является особенностью созревания иммунной системы в раннем возрасте; появляется все больше доказательств того, что экспрессия Th1-цитокинов (IL-1β, IL-8) имеет существенное значение в патогенезе рецидивирующего СБО у детей [10,11].…”