Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

Schmid, Johannes Martin; Würtzen, Peter Adler; Dahl, Ronald; Hoffmann, Hans Jürgen

doi:10.1016/j.jaci.2015.05.023

Cited by 45 publications

(36 citation statements)

References 48 publications

(51 reference statements)

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“…One study demonstrated an association with clinical outcome parameters . Immuno‐solid‐phase allergy chip may also be applicable to monitor the induction of sIgG4 in the updosing phase of SCIT while it shows the application of ISAC in the updosing phase of AIT .…”

Section: Resultsmentioning

confidence: 99%

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper

Shamji

Kappen

Akdiş

et al. 2017

Allergy

300

367

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Background: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. Method: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). Results: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed.

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Section: Resultsmentioning

confidence: 99%

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper

Shamji

Kappen

Akdiş

et al. 2017

Allergy

300

367

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“…The humoral response that marks allergen tolerance induction during AIT is characterized by a transient rise in allergen‐specific IgE followed by a decrease in IgE and a gradual increase in allergen‐specific IgG antibodies. IgG4 particularly increases during the course of AIT linked to continuous administration of the allergen, which results in a 10‐ to 100‐fold decreased ratio of allergen‐specific IgE:IgG4 . IgG4 production has been linked to Breg cells and they are considered as classical non‐inflammatory due to their specific structural and functional features: (i) they do not activate complement, (ii) they display low affinity for Fcγ receptors, and (iii) they are able to exchange Fab arms leading to unique functional bi‐specific monovalent antibodies .…”

Section: Allergen‐specific Immunotherapymentioning

confidence: 99%

“…IgG4 particularly increases during the course of AIT linked to continuous administration of the allergen, which results in a 10-to 100fold decreased ratio of allergen-specific IgE:IgG4. 183,188 IgG4 production has been linked to Breg cells 14 and they are considered as classical non-inflammatory due to their specific structural and functional features: (i) they do not activate complement, (ii) they display low affinity for Fcγ receptors, and (iii) they are able to exchange Fab arms leading to unique functional bi-specific monovalent antibodies. 189 Therefore, anti-inflammatory allergen-specific IgG4 may protect against allergic responses by competing with IgE for allergen binding.…”

Section: Immunologic Mechanisms Operating During Aitmentioning

confidence: 99%

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Palomares

Akdiş

Martín‐Fontecha

2017

Immunological Reviews

260

300

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Allergy is a major public health problem with a high socio-economic impact. The number of allergic patients is expected to reach to four billion within two decades when the World's population reaches to 10 billion. Our knowledge on the molecular mechanisms underlying allergic diseases and allergen tolerance induction had significant advances during the last years. Nowadays, it is well accepted that the generation and maintenance of allergen-specific regulatory T cells (Tregs) and regulatory B cells (Bregs) and the involvement of their suppressive cytokines and surface molecules are essential for the induction of allergen tolerance. These mechanisms play essential roles for the restoration of healthy immune responses to allergens in allergen-specific immunotherapy (AIT) and healthy immune response during high-dose antigen exposure in beekeepers and cat owners. AIT remains as the only disease-modifying and curative treatment for allergic diseases and represents a perfect model to investigate the antigen-specific immune responses in humans. A large number of clinical trials demonstrated AIT as an effective treatment in many patients, but it still faces several drawbacks in relation to efficacy, safety, long duration, and patient adherence. Novel strategies to overcome these inconveniences, such as the development of novel adjuvants and alternative routes of administration are being developed. The better understanding of the molecular mechanism governing the generation of Treg and Breg cells during allergen tolerance might well open new avenues for alternative therapeutic interventions in allergic diseases and help better understanding of other immune-tolerance-related diseases.

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“…Moreover, elevated IgE levels before treatment is thought to be a prerequisite for induction of IgG4 blocking antibodies. In addition IgE and IgG4 levels correlate with other functional immunological changes such as facilitated antigen binding, basophil sensitivity and clinical symptoms score [105]. …”

Section: Treatment Of Chronic Upper Airway Diseasementioning

confidence: 99%

Endotype-driven treatment in chronic upper airway diseases

Greve¹,

Hellings²,

Fokkens³

et al. 2017

Clin Transl Allergy

145

131

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Rhinitis and rhinosinusitis are the two major clinical entities of chronic upper airway disease. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) affect respectively up to 10 and 30% of the total population, hence being associated with an important socio-economic burden. Different phenotypes of rhinitis and CRS have been described based on symptom severity and duration, atopy status, level of control, comorbidities and presence or absence of nasal polyps in CRS. The underlying pathophysiological mechanisms are diverse, with different, and sometimes overlapping, endotypes being recognized. Type 2 inflammation is well characterized in both AR and CRS with nasal polyps (CRSwNP), whereas type 1 inflammation is found in infectious rhinitis and CRS without nasal polyps (CRSsNP). The neurogenic endotype has been demonstrated in some forms of non-allergic rhinitis. Epithelial barrier dysfunction is shown in AR and CRSwNP. Emerging therapies are targeting one specific pathophysiological pathway or endotype. This endotype-driven treatment approach requires careful selection of the patient population who might benefit from a specific treatment. Personalized medicine is addressing the issue of providing targeted treatment for the right patient and should be seen as one aspect of the promising trend towards precision medicine. This review provides a comprehensive overview of the current state of endotypes, biomarkers and targeted treatments in chronic inflammatory conditions of the nose and paranasal sinuses.

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Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

Cited by 45 publications

References 48 publications

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Endotype-driven treatment in chronic upper airway diseases

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