The role of IgG1 and IgG4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy

Strobl, Maria; Demir, Hilal; Acosta, Gabriela Sánchez; Drescher, Axel; Kitzmüller, Claudia; Möbs, Christian; Pfützner, Wolfgang; Bohle, Barbara

doi:10.1016/j.jaci.2023.01.005

Cited by 17 publications

(20 citation statements)

References 33 publications

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“…Here, we employed allergen-specific IgG1 Abs as they dominate IgE-blocking in the early phase of AIT. 5,6 Nevertheless, the correlation of affinity and inhibitory bioactivity also applies to IgG4 because previous work has shown that the isotype is not decisive for IgE-blocking. 7 In summary, this study demonstrates that IgE-blocking bioactivity enhances with both amount and affinity of allergen-specific Ab.…”

Section: Affinity Matters For Ige-blocking Activity Of Allergen-speci...mentioning

confidence: 99%

Affinity matters for IgE‐blocking activity of allergen‐specific antibodies

Strobl

Demir

Stadlmayr

et al. 2023

Allergy

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Section: Affinity Matters For Ige-blocking Activity Of Allergen-speci...mentioning

confidence: 99%

Affinity matters for IgE‐blocking activity of allergen‐specific antibodies

Strobl

Demir

Stadlmayr

et al. 2023

Allergy

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“…Our research corroborated these findings at the transcriptional level. 7,11,20 Our study delineated the intricate landscape of immune cell populations during ICLIT, highlighting alterations in IGHE, IGHA, and IGHGs within memory B cell subsets. The rise of allergen-specific IgG2 and IgG4 through the intermediate allergen-specific IgG1+ memory B cells required CSR.…”

Section: Our Approach To Categorizing B Cells Into Functional Populat...mentioning

confidence: 85%

“…The ICLIT has been demonstrated as a novel, effective treatment through the evaluation of clinical outcomes and total quality of life score with an advantage in efficacy, safety, and patient adherence 15 . Even though the underlying molecular mechanism of AIT has not been fully illustrated, the perspective from immunologists insisted that the induction of immunological tolerance to allergens regulated by allergen‐specific IgE and protective IgG4 as well as IgA play a crucial role in the procedure of AIT 7,11,20 . We herein investigated the primary B cell populations in peripheral blood from an AR patient who underwent ICLIT, using scRNA‐seq to unveil the AIT‐related phenotype with the transcriptome.…”

Section: Discussionmentioning

confidence: 99%

“…10 Moreover, allergen-specific IgG1 as the dominant isotype was revealed to dynamically peak at 12 months after specific allergen AIT. 11 Circulating IL-10-secreting Breg cells were defined as a positive mediator of IgG4 production in humans, potentially suppressing the total, and allergen-specific IgE levels. 12 As yet, pharmaceutical treatment of AR includes local and/or systematic glucocorticoids, antihistamines, leukotriene receptor antagonists, mast cell membrane stabilizers, and anti-IgE monoclonal antibody drugs.…”

Section: Introductionmentioning

confidence: 99%

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Single‐cell RNA sequencing reveals the landscape of biomarker in allergic rhinitis patient undergoing intracervical lymphatic immunotherapy and related pan‐cancer analysis

Li,

Huang

et al. 2024

Environmental Toxicology

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IntroductionAllergic rhinitis (AR) is one of the leading allergic diseases worldwide. Allergen immunotherapy (AIT) induces persistent specific allergen tolerance to achieve remission of the symptoms in AR patients. We creatively conducted the intra‐cervical lymphatic immunotherapy (ICLIT) for AR patients. However, the underlying molecular mechanism of immune cell response of AIT in AR remains elusive.MethodTo investigate the transcriptome profile in AR patients who underwent ICLIT, we comprehensively investigated the transcriptional changes in B cells from peripheral blood mononuclear cells of AR patient by single‐cell RNA sequencing. Immunoglobulins and relative key gene, which influences the B cell differentiation, was demonstrated. The biomarkers' association with different types of tumors was investigated.ResultsNaive B cells, germinal center B cells, activated memory B cells, and memory B cells constituted the B cells subsets. The expression of IGHE, IGHGs, IGHA, IGHD, and IGHM from memory B cells was validated. Pseudotime analysis further indicated the dynamic change from the expression of the immunoglobulins in the memory B cells, suggesting that ITGB1 may contribute to the differentiation procedure of memory B cells. The cell–cell communication among these immune cells demonstrated the significantly enhanced CD23, BTLA signaling after ICLIT in AR patient. ITGB1 was upregulated in 13 tumors and downregulated in six others. High ITGB1 expression was linked to poor prognosis in eight types of tumors. ITGB1 expression showed correlations with tumor mutation burden, tissue purity, and microsatellite instability in different types of tumors.DiscussionITGB1 was demonstrated as a potential biomarker for AR patients after ICLIT and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.

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“…This issue has been addressed by immobilizing the allergen and subsequent incubation with antibodies. [6][7][8] However, the latter approach requires the use of purified antibodies as serum contains a plethora of proteins that could mask allergen-specific binding events. The purification of antibodies may reduce their functionality and often results in low yields.…”

Section: Introductionmentioning

confidence: 99%

Easy assessment of the avidity of polyclonal allergen‐specific serum antibodies

Strobl,

Demir,

Wozniak‐Knopp

et al. 2024

Clin Experimental Allergy

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IntroductionAllergen‐specific IgE‐blocking IgG antibodies contribute to successful allergen immunotherapy (AIT), however, not much is known about their affinity. Since affinity measurements of polyclonal antibodies in serum are technically challenging we evaluated the applicability of acidic disruption of antibody‐allergen complexes by a modified ELISA protocol with monoclonal antibodies (mAbs) specific for the relevant major allergens Betv1 and Mald1. Then, AIT‐induced blocking and non‐blocking Mald1‐specific antibodies in sera from individuals with or without reduced apple allergy were compared.MethodsAfter testing their pH stability coated recombinant allergens were incubated with (i) mAbs diluted in PBS or human serum and (ii) sera from individuals after sublingual administration of Mald1 or Betv1 for 16 weeks. Immune complexes were exposed to buffers in the pH range of 6.4–3.4 and residual antibodies were measured. Avidity indexes (AI), defined as the pH removing 50% of antibodies, were compared to the dissociation constants (KD) of mAbs determined by surface plasmon resonance.ResultsThe selected pH range was applicable to disrupt allergen complexes with highly affine mAbs without compromising allergen integrity. AIs of mAbs accorded with KD values and were unaffected by epitope specificity or the presence of serum proteins. The inter‐assay variability was <4% CV. Protective Mald1‐specific IgG antibodies from individuals with reduced apple allergy showed a higher collective binding strength than that of the non‐protective antibodies of individuals without reduced apple allergy.ConclusionAcidic disruption of allergen‐antibody complexes may be used to estimate the net‐binding force of polyclonal serum antibodies and eases the investigation of affinity‐related research questions in AIT.

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The role of IgG1 and IgG4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy

Cited by 17 publications

References 33 publications

Affinity matters for IgE‐blocking activity of allergen‐specific antibodies

Affinity matters for IgE‐blocking activity of allergen‐specific antibodies

Single‐cell RNA sequencing reveals the landscape of biomarker in allergic rhinitis patient undergoing intracervical lymphatic immunotherapy and related pan‐cancer analysis

Easy assessment of the avidity of polyclonal allergen‐specific serum antibodies

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