Predicting Success of Allergen-Specific Immunotherapy

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.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients

“…Conventional AIT for AR comprises subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), and SLIT is more popular because of its convenience and good tolerability [ 5 , 6 ]. Although SLIT is a safe and effective therapy, many AR patients still do not obtain a satisfactory therapeutic effect, and the rate of recovery fluctuates with a large range [ 7 – 9 ]. Treating patients who respond poorly to SLIT is futile and will lead to a waste of medical resources.…”

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

“…Presently, available treatment options for HDM-induced AR comprise patient education, allergen avoidance, pharmacotherapy, and allergen-specific immunotherapy (AIT) ( Li et al, 2019 ; Zissler and Schmidt-Weber, 2020 ), but HDM AIT is the only effective cure in HDM-induced AR patients through modifying the natural course of disease and inducing immunological tolerance to the causal allergen ( Meteran and Backer, 2019 ; Hoshino et al, 2020 ). AIT can be administrated subcutaneously (SCIT) or sublingually (SLIT), but an increasing number of patients tend to receive SLIT, due to its more convenience and less systemic reactions than those in SCIT ( Li et al, 2018 ; Barker-Tejeda et al, 2020 ).…”

“…AIT can be administrated subcutaneously (SCIT) or sublingually (SLIT), but an increasing number of patients tend to receive SLIT, due to its more convenience and less systemic reactions than those in SCIT ( Li et al, 2018 ; Barker-Tejeda et al, 2020 ). Although SLIT has been demonstrated to be effective in AR, its efficacies differ between patients: some show no benefit even after prolonged treatment ( Liu et al, 2020a ; Zissler and Schmidt-Weber, 2020 ). Previous studies have explored several candidate indicators, such as serum-specific IgE ( Kim et al, 2020 ), periostin ( Hoshino et al, 2020 ), and serum metabolites ( Xie et al, 2021 ), to predict the clinical efficacy of SLIT, but the sensitivity and specificity of these potential biomarkers are not satisfactory.…”

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling

“…Currently, available patient managements for AR include allergen avoidance, medications, and allergen-specific immunotherapy (AIT), and AIT is reported to be the only approach that can alter the natural course of this clinical disorder (11,12). AIT can be performed by subcutaneous (SCIT) or sublingual (SLIT), and growing evidences proved that SCIT was better than SLIT in controlling allergic symptoms, improving compliance and reducing rescue medication consumption (13,14). Although SCIT is a suitable treatment for pediatric AR, not all children respond to this therapy, and the efficacy always fluctuates across users (15)(16)(17).…”