Abstract
BackgroundDespite the effectiveness of allergen immunotherapy (AIT), some patients are unresponsive for reasons still unknown; yet validated response biomarkers remain unavailable. ObjectiveTo analyze immunological parameters as biomarkers to monitor and predict clinical response to a MicroCrystalline Tyrosine-adjuvanted house dust mite (HDM) AIT in patients with allergic rhinitis (AR). MethodsObservational, prospective, multicenter study including adult patients (aged 18–65 years) with AR, with and without asthma, sensitized to the HDM Dermatophagoides pteronyssinus (DP) and prescribed Acarovac Plus® DP 100% in the routine practice. Serum concentrations of total IgE, specific IgE, specific IgG4, IL-4, IL-5, IL-10, IL-13, and IFN-γ were compared between baseline and 12 months after AIT. The relationship between patients’ baseline immunological profiles and classification as low, high, and non-responders and between their sensitization profile to DP allergens and effectiveness were analyzed. ResultsOf 141 patients recruited, 118 (mean [SD] age of 33.6 [9.5] years) were evaluable. One year after treatment, Der p 1-specific IgE, DP-specific IgG4, and IL-10 increased by a mean (SD) of 3.4 (13.6) kU/L (p = 0.016), 0.43 (0.55) mg/L (p < 0.0001), and 1.35 (7.56) pg/mL (p = 0.033), respectively. Non-responders showed increased baseline levels of IL-13 compared to high responders (p = 0.037). Changes in effectiveness variables between baseline and after AIT were similar regardless of the sensitization profile. ConclusionNon-responsive patients to AIT showed increased baseline IL-13 concentrations, suggesting its value as prognostic biomarker. DP-specific AIT increased Der p 1-specific IgE, DP-specific IgG4, and IL-10 concentrations in patients with AR. All patients benefited from treatment regardless of their sensitization profile to major DP allergens.
Highlights
IntroductionAllergic rhinitis (AR) is one of the most prevalent allergic diseases, with an estimated prevalence of 10%–40%.1
We found that increased baseline levels of IL-13, IL-10, and TH2 cytokines were associated with no response, albeit only IL-13 remained significantly different in the multivariate analysis, showing the potential value of IL-13 as predictor of treatment response
Our results obtained from a cohort of patients with allergic rhinitis with and without asthma treated in the real-world setting provide evidence of increased levels of Dermatophagoides pteronyssinus (DP)-sIgG4, Der p 1 sIgE, and IL-10 as mechanisms of immune tolerance induced by allergen immunotherapy (AIT) specific for house dust mite (HDM)
Summary
Allergic rhinitis (AR) is one of the most prevalent allergic diseases, with an estimated prevalence of 10%–40%.1. Effective management of AR entails adequate symptom control and, to this end, current guidelines recommend allergen avoidance and pharmacological treatment.[2,8] in many patients conventional pharmacological treatment may be insufficient; it induces side effects and fails to provide long-term benefits.[9] In contrast, allergen immunotherapy (AIT) targets the underlying cause of the disease by inducing immune tolerance to specific allergens, providing long-term effects and potentially modifying the course of the disease.[10,11,12] Despite the growing evidence about the clinical benefits of AIT, the degree of clinical response varies, being suboptimal in some patients for reasons still unknown.[13,14] In this context, understanding the immunological mechanisms of immune tolerance induced by AIT may enable to identify biomarkers associated with clinical response. Despite the effectiveness of allergen immunotherapy (AIT), some patients are unresponsive for reasons still unknown; yet validated response biomarkers remain unavailable
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