The Human IgE Repertoire

Gadermaier, Elisabeth; Levin, Mattias; Flicker, Sabine; Ohlin, Mats

doi:10.1159/000355947

Cited by 31 publications

(35 citation statements)

References 147 publications

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“…This previous finding is in accordance with several other recent publications (reviewed in Ref. 10) that also found that human IgE repertoires are oligoclonal. However, this finding does not apply to all atopic disease entities.…”

Section: Discussionsupporting

confidence: 93%

Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation

Kerzel

Rogosch

Struecker

et al. 2016

The Journal of Immunology

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The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis.

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Section: Discussionsupporting

confidence: 93%

Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation

Kerzel

Rogosch

Struecker

et al. 2016

The Journal of Immunology

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“…HTS libraries were additionally prepared from cDNA template so that the isotype encoded by each sequence could be identified. The IgE repertoires of these samples revealed relatively few (<150/donor) distinct IgE-encoding rearrangements, compared to rearrangements encoding other isotypes, before initiation of SIT despite the fact that the number of reads per unique sequence was substantially larger for the IgE population in comparison to other isotypes (Supplementary Tables EII–EIV in the Online Repository), in agreement with findings obtained by conventional sequencing approaches (15). …”

Section: Resultssupporting

confidence: 86%

“…Characterization of IgE repertoires in general has been addressed in several studies (reviewed by Gadermaier et al (15)). These pioneering investigations have provided useful insights into the characteristics of IgE repertoires, such as their oligoclonal nature.…”

Section: Introductionmentioning

confidence: 99%

Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy

Levin

King

Glanville

et al. 2016

Journal of Allergy and Clinical Immunology

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Background Specific immunotherapy (SIT) is the only treatment with proven long-term curative potential in allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B cell repertoires are not well understood. Objective To characterize the IgE sequences expressed by allergen-specific B cells, and track the fate of these B cell clones during SIT. Methods We have used high-throughput antibody gene sequencing and identification of allergen-specific IgE using combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and nasal mucosa of aeroallergen-sensitized individuals before and during the first year of subcutaneous SIT. Results Of 52 distinct allergen-specific IgE heavy chains from eight allergic donors, 37 were also detected by high-throughput antibody gene sequencing of blood, nasal mucosa, or both sample types. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. Conclusion Combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies may in the future aid assessment of SIT mechanisms and efficacy.

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“…Furthermore, considering the heterogeneity in the immunological response and the polyclonality of the IgE repertoire (Gadermaier et al, 2014), we decided to perform a study in a large set of patients (n = 79) to attempt to identify the domains of the protein most often involved in IgE recognition.…”

Section: Discussionmentioning

confidence: 99%

“…The major event is the cross-linking of IgE on mast cells and basophils, leading to the release of the inflammatory mediators responsible for the immediate reaction, but other immunological mechanisms involving IgE antibodies have also been described (Acharya et al, 2010;van der Heijden et al, 1993;Ying et al, 2001). However, despite the pivotal role established for IgE in allergic reactions, little is known about the interaction between allergens and antibodies, mainly due to the low concentration of this class of immunoglobulin in the sera of patients and to the fact that IgE-producing B cells have been poorly characterized [reviewed by (Gadermaier et al, 2014)]. Most of the data related to this aspect are derived from in vitro assays using mouse monoclonal antibodies and/or recombinant chimeric human IgE derived from mouse antibodies (Tai et al, 2013;Tiwari et al, 2012).…”

Section: Introductionmentioning

confidence: 99%