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Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy.
Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy. The Journal of allergy and clinical immunology Hoh, R. A., Thörnqvist, L., Yang, F., Godzwon, M., King, J. J., Lee, J. Y., Greiff, L., Boyd, S. D., Ohlin, M. 2023Abstract
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