Abstract
The immune response to antigens is a key aspect of immunology, as it provides opportunities for therapeutic intervention. However, the induction of immunological tolerance is an evolving area that is still not sufficiently understood. Allergen immunotherapy (AIT) is a disease-modulating therapy available for immunoglobulin E (IgE)-mediated airway diseases such as allergic rhinitis or allergic asthma. This disease-modifying effect is not only antigen driven but also antigen specific. The specificity and also the long-lasting, often life-long symptom reduction make the therapy attractive for patients. Additionally, the chance to prevent the onset of asthma by treating allergic rhinitis with AIT is important. The mechanism and, in consequence, therapy guiding biomarker are still in its infancy. Recent studies demonstrated that the interaction of T, B, dendritic, and epithelial cells and macrophages are individually contributing to clinical tolerance and therefore underline the need for a system to monitor the progress and success of AIT. As clinical improvement is often accompanied by decreases in numbers of effector cells in the tissue, analyses of cellular responses and cytokine pattern provide a good insight into the mechanisms of AIT. The suppression of type-2 immunity is accompanied by decreased levels of type-2 mediators such as epithelial CCL-26 and interleukin (IL)-4, IL-13 produced by T cells that are constituting the immune memory and are increasingly controlled by regulatory T and B cells following AIT. Immune tolerance is also associated with increased production of type-1 mediators like interferon-gamma, tissue-homeostating factors like indoleamine 2,3-dioxygenase (IDO) expressed by macrophages and dendritic cells. Although these individual genes were convincingly demonstrated to play a role immune tolerance, they do not predict therapy outcomes of AIT on an individual level. Therefore, combinations or ratios of gene expression levels are a promising way to achieve predictive value and definition of helpful biomarker.
Highlights
Allergen-specific immunotherapy (AIT) is practiced for more than 100 years but the understanding of the cellular and molecular mechanisms just evolved in the last 20 years
The role of the tissue and tissue biomarker in the regulation of tolerance is still insufficiently investigated in AIT, while increasingly recognized as key factor in transplantation tolerance via mechanisms of amino acid consumption [auxotrophy; [42]]
Differentiation of tissue-resident macrophages may provide important information and biomarker of how effective the allergen tolerance has been corrected by allergen-specific immunotherapy [43]
Summary
Allergen-specific immunotherapy (AIT) is practiced for more than 100 years but the understanding of the cellular and molecular mechanisms just evolved in the last 20 years. While quite a few improvements in dosing, adjuvants, allergen extraction, allergen expression, and allergen modification were explored, the main treatment principle is the administration of the antigen into the host. Predicting Success of Allergen Specific Immunotherapy against pathogens, the main target in allergen vaccination is to inhibit an already ongoing immune response. Biomarker that monitor the antigen-specific induction of an immune response are available for conventional vaccination such as antigenspecific immunoglobulins (Ig’s). While the identification of such a marker is very difficult, research has taken smaller steps to approach this predictive biomarker that can be used to decide whether to apply ASIT or not. The smaller steps include marker that indicate whether allergen has been successfully administered (1.1), monitoring of anti-inflammatory effects (1.2), induction of immunosuppressive mechanisms (1.3), and prediction of treatment success following initiation of the treatment (1.4)
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