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

Ramona A. Hoh, Linnea Thörnqvist, Fan Yang, Magdalena Godzwon, Jasmine J. King, Ji Yeun Lee, Lennart Greiff, Scott D. Boyd, Mats Ohlin

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)214-229
Antal sidor16
TidskriftJournal of Allergy and Clinical Immunology
Volym152
Nummer1
DOI
StatusPublished - 2023

Ämnesklassifikation (UKÄ)

  • Lungmedicin och allergi

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