Abstract

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.To characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies undergoing SIT.Allergen-specific IgE-expressing clones were identified using combinatorial scFv libraries and tracked in PBMC and nasal biopsies over a 3-year period with antibody gene repertoire sequencing. Characteristics of private IgE-expressing clones were compared with those of stereotyped or "public" IgE responses to the grass pollen allergen Phl p 2.Members of the same allergen-specific IgE lineages were observed in nasal biopsies and blood, and lineages detected at baseline persisted in blood and nasal biopsies after 3 years of SIT, including B cells that express IgE. Evidence of progressive class-switch recombination (CSR) 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 scFv-derived allergen-specific sequences or IgE sequences of unknown specificity.Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE+ clones demonstrates persistence of allergen-specific IgE+ clones, progressive CSR to IgG subtypes, and distinct maturation of a stereotyped Phl p 2-clonotype.

View details for DOI 10.1016/j.jaci.2023.02.009

View details for PubMedID 36828082