Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy

Hoh, Ramona A. ; Thörnqvist, Linnea LU ; Yang, Fan ; Godzwon, Magdalena LU ; King, Jasmine J. ; Lee, Ji Yeun ; Greiff, Lennart LU ; Boyd, Scott D. and Ohlin, Mats LU orcid (2023) In Journal of Allergy and Clinical Immunology 152(1). p.214-229
Abstract

Background: Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Objective: Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Methods: Allergen-specific IgE–expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private... (More)

Background: Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Objective: Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Methods: Allergen-specific IgE–expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private IgE-expressing clones were compared with those of stereotyped or “public” IgE responses to the grass pollen allergen Phleum pratense (Phl p) 2. Result: Members of the same allergen-specific IgE lineages were observed in nasal biopsy samples and blood, and lineages detected at baseline persisted in blood and nasal biopsy samples after 3 years of SIT, including B cells that express IgE. Evidence of progressive class switch recombination to IgG subclasses was observed after 3 years of SIT. A common stereotyped Phl p 2–specific antibody heavy chain sequence was detected in multiple donors. The amino acid residues enriched in IgE-stereotyped sequences from seropositive donors were analyzed with machine learning and k-mer motif discovery. Stereotyped IgE sequences had lower overall rates of somatic hypermutation and antigen selection than did single-chain variable fragment–derived allergen-specific sequences or IgE sequences of unknown specificity. Conclusion: Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE+ clones demonstrates persistence of allergen-specific IgE+ clones, progressive class switch recombination to IgG subtypes, and distinct maturation of a stereotyped Phl p 2 clonotype.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aeroallergens, allergen-specific antibodies, clonotype evolution, IgE, IgG, immunoglobulin repertoire, isotype class switch, local immunity, specific immunotherapy, stereotyped immunoglobulin rearrangement
in
Journal of Allergy and Clinical Immunology
volume
152
issue
1
pages
16 pages
publisher
Elsevier
external identifiers
  • pmid:36828082
  • scopus:85152705169
ISSN
0091-6749
DOI
10.1016/j.jaci.2023.02.009
language
English
LU publication?
yes
id
41a372cd-0c05-4d9f-b67b-e0749a6da00a
date added to LUP
2023-07-19 10:54:56
date last changed
2024-04-19 23:40:30
@article{41a372cd-0c05-4d9f-b67b-e0749a6da00a,
  abstract     = {{<p>Background: Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Objective: Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Methods: Allergen-specific IgE–expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private IgE-expressing clones were compared with those of stereotyped or “public” IgE responses to the grass pollen allergen Phleum pratense (Phl p) 2. Result: Members of the same allergen-specific IgE lineages were observed in nasal biopsy samples and blood, and lineages detected at baseline persisted in blood and nasal biopsy samples after 3 years of SIT, including B cells that express IgE. Evidence of progressive class switch recombination to IgG subclasses was observed after 3 years of SIT. A common stereotyped Phl p 2–specific antibody heavy chain sequence was detected in multiple donors. The amino acid residues enriched in IgE-stereotyped sequences from seropositive donors were analyzed with machine learning and k-mer motif discovery. Stereotyped IgE sequences had lower overall rates of somatic hypermutation and antigen selection than did single-chain variable fragment–derived allergen-specific sequences or IgE sequences of unknown specificity. Conclusion: Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE<sup>+</sup> clones demonstrates persistence of allergen-specific IgE<sup>+</sup> clones, progressive class switch recombination to IgG subtypes, and distinct maturation of a stereotyped Phl p 2 clonotype.</p>}},
  author       = {{Hoh, Ramona A. and Thörnqvist, Linnea and Yang, Fan and Godzwon, Magdalena and King, Jasmine J. and Lee, Ji Yeun and Greiff, Lennart and Boyd, Scott D. and Ohlin, Mats}},
  issn         = {{0091-6749}},
  keywords     = {{Aeroallergens; allergen-specific antibodies; clonotype evolution; IgE; IgG; immunoglobulin repertoire; isotype class switch; local immunity; specific immunotherapy; stereotyped immunoglobulin rearrangement}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{214--229}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Allergy and Clinical Immunology}},
  title        = {{Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy}},
  url          = {{http://dx.doi.org/10.1016/j.jaci.2023.02.009}},
  doi          = {{10.1016/j.jaci.2023.02.009}},
  volume       = {{152}},
  year         = {{2023}},
}