Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy.
Aeroallergens
IgE
IgG
allergen-specific antibodies
clonotype evolution
immunoglobulin repertoire
isotype class switch
local immunity
specific immunotherapy
stereotyped immunoglobulin rearrangement
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
02
08
2022
revised:
22
01
2023
accepted:
09
02
2023
medline:
10
7
2023
pubmed:
25
2
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE
Sections du résumé
BACKGROUND
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
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
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
RESULTS
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
CONCLUSIONS
Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE
Identifiants
pubmed: 36828082
pii: S0091-6749(23)00223-3
doi: 10.1016/j.jaci.2023.02.009
pii:
doi:
Substances chimiques
Single-Chain Antibodies
0
Allergens
0
Immunoglobulin E
37341-29-0
Immunoglobulin G
0
Plant Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
214-229Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.