Heterogeneous origin of IgE in atopic dermatitis and psoriasis revealed by B cell receptor repertoire analysis

Lihua Luo; Yang Luo; Jing Xu; Ronghui Zhu; Jinghua Wu; Xiao Liu; Wei Li; Xu Yao

doi:10.1111/all.15173

Heterogeneous origin of IgE in atopic dermatitis and psoriasis revealed by B cell receptor repertoire analysis

Allergy. 2022 Feb;77(2):559-568. doi: 10.1111/all.15173. Epub 2021 Nov 12.

Authors

Lihua Luo^{1

2}, Yang Luo³, Jing Xu¹, Ronghui Zhu¹, Jinghua Wu², Xiao Liu⁴, Wei Li^{1

5}, Xu Yao³

Affiliations

¹ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
⁴ Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
⁵ Department of Allergy, Huashan Hospital, Fudan University, Shanghai, China.

PMID: 34738638
DOI: 10.1111/all.15173

Abstract

Background: Epicutaneous sensitization is an important route for the production of IgE, and skin inflammation-induced IgE has recently been reported having features of natural antibody. Atopic dermatitis (AD) and psoriasis have differentially increased level of serum IgE; however, the production mechanism of IgE in these inflammatory skin diseases remains unknown.

Objective: To explore the origin of IgE in AD and psoriasis by analyzing the B cell receptor repertoire.

Methods: mRNA was prepared from peripheral blood mononuclear cells of AD and psoriasis patients that had elevated serum levels of IgE, and immunoglobulin heavy chain (IGH) repertoires were sequenced after reverse transcription. Clonal lineages of B cells containing members expressing IgE were identified, and somatic hypermutations in IGH inherited from common ancestors within the clonal lineage were used to infer the relationships between B cells.

Results: The proportions of IGHE from AD and psoriasis were higher than that of normal control, which were positively correlated with the levels of serum total IgE. The somatic hypermutation value of IGHE variable region was lower than that of IGHG and IGHA, but higher than IGHM and IGHD, indicating a mixed natural and adaptive origins of IgE; and psoriasis demonstrated lower level of hypermutation than AD. The Shannon indexes of CDR3 in IGHE of AD and psoriasis were higher than that of normal control, also supporting the natural origin. The VH usage of IgE was weakly biased in AD and psoriasis patients with high level of house dust mite-specific IgE. Comparison of the number of shared mutations in multi-isotype lineages containing IgE showed that isotype-switching from IgG-expressing B cells might be the major source of IgE in AD and psoriasis.

Conclusion: IgE has heterogeneous origin in AD and psoriasis, and skin inflammation may contribute to the increased production of natural IgE.

Keywords: IgE; atopic dermatitis; immune repertoire; natural antibody; psoriasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dermatitis, Atopic*
Humans
Immunoglobulin E
Inflammation
Leukocytes, Mononuclear
Psoriasis* / genetics
Receptors, Antigen, B-Cell

Substances

Receptors, Antigen, B-Cell
Immunoglobulin E