The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias

Lim, Annick; Luderschmidt, S; Weidinger, Anke; Schnopp, Christina; Ring, Johannes; Hein, Rüdiger; Ollert, Markus; Mempel, Martin

doi:10.1016/j.jaci.2007.05.035

Cited by 37 publications

(33 citation statements)

References 36 publications

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“…An excessive usage of V H families that are normally infrequently used in secondary immune responses might hence be indicative of a superantigen-like activation of B cells (1). However, not all studies on immunogenetic characteristic of the IgE response in atopic eczema found a biased V H usage (7,8).…”

Section: Discussionmentioning

confidence: 96%

“…Although some of these aspects have already been addressed in studies with adult patients [ (7)(8)(9), reviewed in Refs. 1 and 10], hitherto the molecular characteristics of the IgE response have not been analyzed systematically in children with atopic dermatitis, even though this specific age group is of particular interest for the evolvement of the IgE response in atopic dermatitis.…”

Section: Mmunoglobulin E Is a Central Effector Molecule In Allergymentioning

confidence: 99%

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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: Discussionmentioning

confidence: 96%

Section: Mmunoglobulin E Is a Central Effector Molecule In Allergymentioning

confidence: 99%

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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“…This is particularly interesting in the context of allergen-specific immunotherapy and the emerging anti-IgE therapy, which has redirected the spotlight in allergy treatment to the B cell (1). In a recent study, Lim et al (3) showed that the IgE repertoire in patients with atopic dermatitis follows a similar variable gene segment of the H Ig chain (V H ) gene family usage pattern as other Ig isotypes. Davies and O'Hehir (4) found indication that the IgE response could be oligoclonal and Ag-driven.…”

mentioning

confidence: 99%

“…This approach is challenging because IgE-producing plasma cells are extremely rare (14). Therefore, most such studies chose patients with atopic dermatitis with extremely high IgE titers (3,9). We have recently found indication that the IgE response might differ between allergic sensitization and helminth infection (15), but it is still unknown if the IgE response also differs between different allergic disease entities (e.g., allergic asthma, allergic rhinitis, atopic dermatitis).…”

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confidence: 99%

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IgE Transcripts in the Circulation of Allergic Children Reflect a Classical Antigen-Driven B Cell Response and Not a Superantigen-Like Activation

Kerzel

Rogosch

Struecker

et al. 2010

The Journal of Immunology

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Allergic asthma is the most frequent chronic disorder in childhood. Although IgE is a central effector molecule in allergic diseases, the nature of the IgE response is still under debate. The objective of our study was to clarify whether the IgE repertoire in the circulation of allergic children represents a classical Ag-driven and oligoclonal B cell response, a superantigen-like activation of a subset of B cells, or a polyclonal B-1 cell expansion. Using a highly sensitive RT-PCR method, we amplified, cloned, and sequenced IgE H chain transcripts from 13 children with allergic asthma. We gained 1366 functional IgE sequences, which currently represent the most extensive collection of human IgE transcripts. Compared to IgM transcripts from the same children, the somatic mutation rate was significantly enhanced in IgE transcripts (21‰ versus 72‰; p < 0.001), which renders a polyclonal B-1 response unlikely. Moreover, IgE sequences displayed significantly enhanced Ag selection and hence were indicative of a classical Ag-driven immune response with affinity maturation (p < 0.001). In contrast to several recent studies, the usage pattern of variable gene segment of the H Ig chain in IgE transcripts followed the germline complexity, arguing against a superantigen-like interaction. We conclude that IgE transcripts in the circulation of children with allergic asthma reflect a classical adaptive B-2 cell response. This study provides reference data for a better characterization of the IgE response under immunomodulating therapies, such as anti-IgE therapy or allergen-specific immunotherapy.

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Special Therapeutic Options and Substances in the Treatment of Atopic Eczema

Ring¹

2016

Atopic Dermatitis

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The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias

Cited by 37 publications

References 36 publications

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

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

IgE Transcripts in the Circulation of Allergic Children Reflect a Classical Antigen-Driven B Cell Response and Not a Superantigen-Like Activation

Special Therapeutic Options and Substances in the Treatment of Atopic Eczema

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