Allergen-Specific IgE and IgG4 as Biomarkers for Immunologic Changes during Subcutaneous Allergen Immunotherapy

(1) Background: Biomarkers of efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis have not been evaluated in details. The present study aims to assess the relevance of measuring of sIgE, sIgG4 and IgE/IgG4 ratio during SCIT in patients with allergic rhinitis; (2) Methods: 20 patients, 13 men and 7 women aged 19 to 58 years, with clinically manifested seasonal and perennial allergic rhinitis were studied. At the initiation and in the end of the three-year course of SCIT serum allergen-specific IgE and IgG4 were measured with ImmunoCAP system. The sIgE/sIgG4 ratio was calculated as a biomarker for immunologic effectiveness; (3) Results: There was a significant increase of sIgG4 antibodies (p < 0.05), while at the end of SCIT for the sIgE levels no significant changes were seen (p > 0.05). Moreover, 90% of patients showed a decrease of the IgE/IgG4 ratio; (4) Conclusions: In most of treated patients with AR, SCIT with Bulgarian allergen products leads to clear immunological changes. After a 3-year of SCIT there is a significant increase in allergen specific IgG4 levels and both decrease of sIgE and IgE/IgG4 ratio. sIgE, sIgG4 and IgE/IgG4 ratio can be used as a substantial biomarker for predicting immunological effectiveness of SCIT.

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The IgE Blocking Activity Induced by Dermatophagoides pteronyssinus Subcutaneous Immunotherapy Does Not Correlate with Specific IgA but with IgG4 in both Serum and Saliva

International Archives of Allergy and Immunology ◽

10.1159/000517152 ◽

2021 ◽

pp. 1-14

Author(s):

Yong He ◽

Jinling Liu ◽

Deyu Zhao ◽

Suqin Zhang ◽

Guodong Hao ◽

...

Keyword(s):

Treatment Time ◽

Symptomatic Treatment ◽

Specific Ige ◽

Dermatophagoides Pteronyssinus ◽

Subcutaneous Immunotherapy ◽

Control Group ◽

Serum Igg4 ◽

Specific Igg4 ◽

Blocking Activity ◽

Der P 2

Background: The role of salivary-specific IgG4 and IgA in subcutaneous immunotherapy (SCIT) is not well defined. We aimed to investigate the change of IgG4 and IgA in both serum and saliva and their correlations with IgE-blocking-factor (IgE-BF) during SCIT. Method: 307 Dermatophagoides pteronyssinus (DP) allergic rhinitis and/or asthma patients were recruited for this study. 286 patients received DP-SCIT for 1 year. Twenty-one patients received only symptomatic treatment. DP-, Der p 1-, and Der p 2-specific IgE in serum, specific-IgG4 and Der p 2-specific IgA1 and IgA2 in both serum and saliva were measured at timepoints 0, 4, and 12 months during DP-SCIT. Correlation between salivary and serological IgG4, IgA, and their correlation with DP-specific IgE-BF measured in serum was evaluated. Results: During DP-SCIT, the allergen-specific IgG4 in both saliva and serum increased and correlated significantly, the correlation becomes stronger over the treatment time. DP-specific IgE-BF significantly correlated with DP-specific IgG4 in serum (p < 0.0001) at different timepoints and in saliva at 12 months of SCIT (p < 0.01). No change in Der p 2-specific IgA during DP-SCIT was observed, and the IgA in serum did not correlate with IgA in saliva. There was no correlation between DP IgE-BF and Der p 2-specific IgA in serum or saliva. The control group did not exhibit significant changes in any antibody level measured. Conclusion: The IgE blocking activity induced by DP-SCIT treatment correlated with specific IgG4 and not IgA. The IgG4 in saliva correlates with serum IgG4 and can be an alternative immunological marker beyond 1 year of SCIT treatment.

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Recent advances in allergic rhinitis

F1000Research ◽

10.12688/f1000research.15367.1 ◽

2018 ◽

Vol 7 ◽

pp. 1333 ◽

Cited By ~ 16

Author(s):

Flavia C. L. Hoyte ◽

Harold S. Nelson

Keyword(s):

Allergic Rhinitis ◽

Work Productivity ◽

Allergen Challenge ◽

Economic Cost ◽

Symptomatic Treatment ◽

The United States ◽

Specific Ige ◽

Subcutaneous Immunotherapy ◽

Nasal Allergy

Allergic rhinitis affects 20 to 30% of adults in both the United States and Europe and perhaps a somewhat higher percentage of children. In addition to nasal and ocular symptoms directly related to the allergic process, interference of these symptoms with sleep leads to daytime sleepiness and impaired quality of life. Patients miss work because of symptoms but an even greater problem is interference with work productivity, or presenteeism, which has been reported to be the biggest contributor to the total economic cost of allergic rhinitis. There has been increasing awareness that many patients with either seasonal or perennial symptoms but negative skin and in vitro tests for allergen sensitivity have local nasal allergy, diagnosable by the presence of allergen-specific IgE in their nasal secretions or a positive nasal allergen challenge or both. The pharmaceutical management of allergic rhinitis rests on symptomatic treatment with antihistamines that perhaps are more effectively administered intranasally than orally and intranasal corticosteroids. Allergen immunotherapy is very effective, even for local allergic rhinitis, and the shortcomings of subcutaneous immunotherapy of inconvenience and safety are reduced by the introduction of sublingual immunotherapy (SLIT). Use of the latter is currently somewhat limited by the lack of appropriate dosing information for SLIT liquids and the limited number of allergens for which SLIT tablets are available.

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Skin Prick Test and Serum Specific IgE May Not Be Sufficient for the Diagnosis of Perennial Allergic Rhinitis in Atopic Patients

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2012.12.829 ◽

2013 ◽

Vol 131 (2) ◽

pp. AB41

Author(s):

Miguel Blanca ◽

Carmen Rondon ◽

Paloma Campo ◽

Francisca Gomez ◽

Rosa García Mendoza ◽

...

Keyword(s):

Allergic Rhinitis ◽

Skin Prick Test ◽

Specific Ige ◽

Perennial Allergic Rhinitis ◽

Prick Test

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Allergen immunotherapy for seasonal and perennial allergic rhinitis

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.1993.tb00378.x ◽

1993 ◽

Vol 23 (s3) ◽

pp. 3-6 ◽

Cited By ~ 2

Keyword(s):

Allergic Rhinitis ◽

Allergen Immunotherapy ◽

Perennial Allergic Rhinitis

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Suplatast Tosilate affects the Initial Increase in Specific IgE and Interleukin-4 during Immunotherapy for Perennial Allergic Rhinitis

Acta Oto-Laryngologica ◽

10.1080/00016489850182846 ◽

1998 ◽

Vol 118 (538) ◽

pp. 126-132 ◽

Cited By ~ 3

Author(s):

Yushi Washio, Yoshihiro Ohashi, Ayaki Tan

Keyword(s):

Allergic Rhinitis ◽

Specific Ige ◽

Interleukin 4 ◽

Initial Increase ◽

Perennial Allergic Rhinitis

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Allergen Immunotherapy in Pediatric Respiratory Allergy

Current Treatment Options in Allergy ◽

10.1007/s40521-021-00280-4 ◽

2021 ◽

Author(s):

Ali Doroudchi ◽

Kamran Imam ◽

Maria Ines Garcia Lloret

Keyword(s):

Allergic Rhinitis ◽

Allergic Asthma ◽

Allergen Immunotherapy ◽

Treatment Options ◽

Disease Process ◽

House Dust Mites ◽

Subcutaneous Immunotherapy ◽

Activation Markers ◽

Safety And Efficacy ◽

Asthma In Children

Abstract Purpose of Review Atopic diseases such as asthma and allergic rhinitis are highly prevalent in children. Common triggers include tree and grass pollens, house dust mites, molds, and animal dander. These diseases are most often treated symptomatically; however, many patients show partial or poor response and require long-term medication use. Allergen immunotherapy (AIT) stands as the only treatment modality that can alter the underlying disease process and potentially offer a cure. In this review article, we discuss the merits of AIT with particular emphasis on its efficacy and safety in pediatric patients. We also discuss the challenges for AIT implementation and present an overview of current research that aims at improving its applicability for the treatment of allergic diseases. Recent Findings Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both safe and efficacious treatment options in children with allergic rhinitis and allergic asthma. Additionally, AIT has efficacy in preventing the development of asthma in children. Although there are clear advantages with AIT, there are challenges to overcome to optimize treatment. Solutions include improved diagnostics with pre-treatment biomarkers and molecular multiplex assays, biomarkers for prediction of response (e.g., basophil activation markers), improved allergen immunogenicity with the use of recombinant AIT, adjuvants, and allergoids, and lastly improved safety with the concurrent use of omalizumab. Summary AIT has shown safety and efficacy in major clinical trials for the treatment of allergic rhinitis and allergic asthma in children. AIT provides a curative treatment option for atopic disorders and should be considered in children with allergic rhinitis and allergic asthma. There are many continued advances being made in the field of allergy to further improve the safety and efficacy profile and shorten the duration of AIT treatment.

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Role of Allergen Immunotherapy in Asthma Treatment and Asthma Development

Allergies ◽

10.3390/allergies1010003 ◽

2020 ◽

Vol 1 (1) ◽

pp. 33-45

Author(s):

Kazuyuki Nakagome ◽

Makoto Nagata

Keyword(s):

Allergic Rhinitis ◽

Allergen Immunotherapy ◽

Clinical Symptoms ◽

Remission Rate ◽

Allergic Diseases ◽

Natural Course ◽

Atopic Asthma ◽

Subcutaneous Immunotherapy ◽

Conventional Drug ◽

Moderate Disease

Allergen immunotherapy may modify the natural course of allergic diseases and induce remission. It includes subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). For asthma, allergen immunotherapy using house dust mite (HDM) improves clinical symptoms and airway hyperresponsiveness and decreases drug requirements. Furthermore, it has been suggested that allergen immunotherapy also has the following effects: (1) the effect can be maintained for more than a year even if the treatment is terminated, (2) the remission rate of childhood asthma can be increased, (3) new allergen sensitization can be suppressed, and (4) asthma development can be prevented if allergen immunotherapy was performed in the case of pollinosis. Allergen immunotherapy differs from conventional drug therapy, in particular the effect of modifying the natural course of allergic diseases and the effect of controlling complicated allergic diseases such as rhinoconjunctivitis. The general indication for HDM-SCIT in asthma is HDM-sensitized atopic asthma with mild-to-moderate disease and normal respiratory function. HDM allergens should be involved in the pathogenesis of asthma, and a duration of illness of less than 10 years is desirable. HDM-SLIT is available for allergic rhinitis but not for asthma in Japan. However, as the efficacy of SLIT for asthma has been fully proven internationally, SLIT is also applied in asthmatics with complicated allergic rhinitis in Japan.

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Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy

Frontiers in Immunology ◽

10.3389/fimmu.2020.559746 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ting-Ting Ma ◽

Meng-Da Cao ◽

Rui-Li Yu ◽

Hai-Yun Shi ◽

Wei-Jun Yan ◽

...

Keyword(s):

Allergic Rhinitis ◽

Regression Analysis ◽

Immunosorbent Assay ◽

Allergen Immunotherapy ◽

Specific Ige ◽

Enzyme Linked Immunosorbent Assay ◽

Potential Biomarker ◽

Before And After ◽

Leukotriene A4 ◽

Potential Biomarkers

BackgroundAllergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. MethodsArtemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders.ResultsArtemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT.ConclusionSerum LTA4H may be a potential biomarker for early prediction of an effective AIT.

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