Real-world evidence and biomarkers in allergic diseases

In this month's editorial, the Editors of the journal have highlighted three interesting studies that are included in this issue. The first article provides evidence that subcutaneous immunotherapy using pollen allergoid tyrosine adsorption can have long-term clinical benefits for individuals with allergic rhinitis (AR) and asthma (AA).¹ Allergoid tyrosine-adsorbed subcutaneous immunotherapy is a highly recommended treatment for several reasons. The treatment is personalised to an individual's specific allergic triggers, which means it provides targeted treatment. This therapy has been proven to effectively reduce allergy symptoms and enhance the quality of life for many patients. Moreover, the modified allergens used in the therapy are less likely to cause severe allergic reactions compared to unmodified allergens. Immunotherapy is a long-lasting solution for allergy symptoms. It addresses the underlying cause of allergies rather than just managing the symptoms.^{2, 3}

In a retrospective study conducted by Vogelberg et al., the impact of allergen immunotherapy (AIT) on AR progression and the onset of the need for AA medication was analysed using a German database that covered around 35% of national prescriptions from 2008 to 2020. The study was funded by an AIT manufacturer. Prescription data of AR patients aged between 5 and 65 years, who were treated with grass or tree pollen AIT between 2009 and 2013, were evaluated. These patients were followed for at least 2 years after AIT cessation and were compared with matched control patients with seasonal AR. All the prescription data was anonymized. The study found that fewer patients who received AIT treatment were prescribed symptomatic AR medication and AA medication compared to the control group. The prescriptions for AR and AA medications for AIT patients were reduced during the follow-up period compared to baseline and controls. The study found all endpoints to be significant for both children/adolescents and adults in stratified analyses. The latest data from observations has shown that immunotherapy is associated with better long-term health outcomes. This means that patients who undergo immunotherapy can expect to have improved health over time. The findings offer hope for those seeking effective treatment for chronic illnesses, and more research in this area is encouraged (Figure 1).

This issue's second editor's choice article explores the use of novel state-of-the-art proteomic analysis to identify biomarkers of asthma. In this elegant study by Hastie and colleagues,⁴ a comprehensive protein analysis on a large cohort of asthmatics was performed to interrogate the molecular phenotypes of severe and non-severe asthma. The level of 75 inflammatory proteins was quantified in the bronchoalveolar lavage fluid (BALF)⁵ from 48 severe and 77 non-severe adult asthmatics, which was then validated in the sputum. A repertoire of eight proteins in the BALF was significantly increased, whilst seven proteins were decreased in severe asthma compared to non-severe asthma. Machine learning algorithms identified FGF2, PDGFaa and CXCL7 as the most important variables in distinguishing asthma severity within the cohort. They confirmed altered airway remodelling and differential cytokine-chemokine signalling within the airways of severe asthmatics compared to non-severe asthmatics. Findings from this study not only highlight potential biomarkers of severity which can be used to better phenotype patients in the clinical setting but also suggest novel therapeutic targets for asthma (Figure 2).

Induction of allergen-specific IgG antibodies following a successful AIT has been reported over the years,^{6, 7} though little has been explored in terms of their affinity. Until recently, affinity measurements of polyclonal antibodies in serum remained a technical challenge for most researchers and pose a key unanswered question for researchers within the field, as to the role of antibody affinity in tolerance induction following AIT. In the final Editor's Choice article, the authors, a novel assay was introduced by Strobl et al.⁸ which addresses challenges to this specific aspect. The authors introduced a modified ELISA protocol that utilised complexes of monoclonal antibodies that were dissociated with acidic buffers. The study compared AIT-induced blocking and non-blocking Mald1-specific antibodies in sera from individuals with or without reduced apple allergy on the modified ELISA. The study demonstrated higher collective binding strength from protective Mald1-specific IgG antibodies from individuals with reduced apple allergy compared to non-protective antibodies obtained from individuals without reduced apple allergy. This highlights the importance of acidic dissociation in estimating the net-binding force of allergen-specific polyclonal IgG antibodies in serum, allowing its potential use to facilitate studies on the role of antibody affinity following AIT.

MHS and RJB drafted and finalised the manuscript.

The authors declare no conflict of interests.