Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/pai.13189

EAACI Allergen Immunotherapy User's Guide.

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.14582

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/alr.23090

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Allergic rhinitis (AR) is a chronic inflammatory immunoglobulin (Ig) E-mediated disease of the nasal mucosa that can be triggered by the inhalation of seasonal or perennial allergens. Typical symptoms include sneezing, rhinorrhea, nasal itching, nasal congestion and symptoms of allergic conjunctivitis. AR affects a quarter of the population in the United States of America and Europe. AR has been shown to reduce work productivity in 36–59% of the patients with 20% reporting deteriorated job attendance. Moreover, 42% of children with AR report reduced at-school productivity and lower grades. Most importantly, AR impacts the patient’s quality of life, due to sleep deprivation. However, a proportion of patients fails to respond to conventional medication and opts for the allergen immunotherapy (AIT), which currently is the only disease-modifying therapeutic option. AIT can be administered by either subcutaneous (SCIT) or sublingual (SLIT) route. Both routes of administration are safe, effective, and can lead to tolerance lasting years after treatment cessation. Both innate and adaptive immune responses that contribute to allergic inflammation are suppressed by AIT. Innate responses are ameliorated by reducing local mast cell, basophil, eosinophil, and circulating group 2 innate lymphoid cell frequencies which is accompanied by decreased basophil sensitivity. Induction of allergen-specific blocking antibodies, immunosuppressive cytokines, and regulatory T and B cell phenotypes are key pro-tolerogenic adaptive immune responses. A comprehensive understanding of these mechanisms is necessary for optimal selection of AIT-responsive patients and monitoring treatment efficacy. Moreover, it could inspire novel and more efficient AIT approaches.

/pdf/mechanisms-of-allergen-immunotherapy-in-allergic-rhinitis-3vqplawzu9.pdf

Mechanisms of Allergen Immunotherapy in Allergic Rhinitis.

Allergen-specific immunotherapy (AIT) is an allergen-specific form of treatment for patients suffering from immunoglobulin E (IgE)-associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease-causing allergen with the goal to induce a protective immunity consisting of allergen-specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long-lasting protection and prevents the progression of disease to severe manifestations. AIT is cost effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development, and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/all.14300

Past, present, and future of allergen immunotherapy vaccines.

Allergen-specific immunotherapy for house dust mite allergy is effective, but there are no validated biomarkers reflecting or predicting the clinical efficacy. We aimed to investigate the relationship between clinical outcomes and functional responses of allergen-specific IgG4 (sIgG4) and specific IgE (sIgE) during Dermatophagoides pteronyssinus s.c. allergen immunotherapy (SCIT) in allergic rhinitis and/or asthma patients. Combined symptom medication scores (SMS), D. pteronyssinus-sIgG4 levels, D. pteronyssinus-sIgE levels, and the serum inhibitory capacity against D. pteronyssinus-sIgE facilitated allergen binding to B cells (IgE-FAB) were determined during the updosing (week 0, 4, 12, and 16) and maintenance (week 52, 104, and 156) phase of SCIT. We found that SCIT patients had a significant improvement in SMS from week 52 to 156 compared with medication-treated control subjects (p < 0.05). Levels of D. pteronyssinus-sIgG4 in SCIT patients showed a significant increase from week 12 to 156 (p < 0.05). Serum obtained from SCIT patients significantly inhibited D. pteronyssinus-sIgE binding to B cells after 16 wk (p < 0.01). Significantly lower levels of D. pteronyssinus-sIgE were observed in SCIT patients after 52 wk (p < 0.05). A significant relationship was demonstrated between SMS and IgE-FAB or D. pteronyssinus-sIgG4 during the maintenance phase according to linear regression analysis. In conclusion, D. pteronyssinus-sIgG4 level and D. pteronyssinus IgE-FAB are associated with clinical efficacy in the maintenance phase rather than the updosing phase of SCIT. Immunologic tolerance can be induced with SCIT when maintenance phase is achieved.

Functional and Immunoreactive Levels of IgG4 Correlate with Clinical Responses during the Maintenance Phase of House Dust Mite Immunotherapy

It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)-allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.

/pdf/allergen-immunotherapy-induced-immunoglobulin-g4-reduces-47q4jitwui.pdf

Allergen Immunotherapy-Induced Immunoglobulin G4 Reduces Basophil Activation in House Dust Mite-Allergic Asthma Patients.

The efficacy of allergen immunotherapy (AIT) has been reported with different allergens including house dust mites (HDM). HDM are the most prevalent allergens in patients with asthma and/or rhinitis in China. In addition to improving symptoms, reducing medication need, and improving quality of life, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. To date, the use of AIT is becoming more acceptable in China, and there are many studies about the current clinical practice immunotherapy. In this paper we discuss the main aspects of AIT undertaken in China; including symptom and medication scores, pulmonary function and airway hyperresponsiveness, specific allergen sensitivity, safety evaluation, and mechanisms underlying AIT. This review will provide some important information on AIT treatment strategies to doctors, healthcare professionals and organizations involved in the AIT in China. According to the studies in China, successful AIT may induce antibody responses and cellular reactions in relation to the significant improvement in clinical symptoms, reducing the need for medications and maintenance of stable pulmonary functions.

/pdf/house-dust-mite-subcutaneous-immunotherapy-in-chinese-44ig3meyaa.pdf

House dust mite subcutaneous immunotherapy in Chinese patients with allergic asthma and rhinitis

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Functional and Immunoreactive Levels of IgG4 Correlate with Clinical Responses during the Maintenance Phase of House Dust Mite Immunotherapy

Allergen Immunotherapy-Induced Immunoglobulin G4 Reduces Basophil Activation in House Dust Mite-Allergic Asthma Patients.

House dust mite subcutaneous immunotherapy in Chinese patients with allergic asthma and rhinitis