Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy
(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.
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- author
- 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
- organization
- publishing date
- 2023
- 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}}, }