The following is a summary of “Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy,” published in the JULY 2023 issue of Allergy & Immunology by Hoh, et al.
For a study, researchers sought to investigate the characteristics of IgE sequences expressed by allergen-specific B cells in patients with aero-allergies undergoing specific immunotherapy (SIT) over a 3-year longitudinal period.
Combinatorial single-chain variable fragment libraries were used to identify allergen-specific IgE-expressing clones. The clones were tracked in peripheral blood mononuclear cells (PBMCs) and nasal biopsy samples of patients undergoing SIT for 3 years using antibody gene repertoire sequencing. Private IgE-expressing clones were compared to stereotyped or “public” IgE responses specific to the grass pollen allergen Phleum pratense (Phl p) 2.
The study found that allergen-specific IgE lineages were present in nasal biopsy samples and the patients’ blood. After three years of SIT, the same lineages identified at baseline, including B lymphocytes producing IgE, were still present in blood and nasal biopsy samples. After three years of SIT, evidence of increasing class switch recombination to IgG subclasses was also discovered. Multiple donors shared a common stereotyped Phl p 2-specific antibody heavy chain sequence. Machine learning and k-mer motif discovery analyses revealed that stereotyped IgE sequences had lower overall somatic hypermutation and antigen selection rates than single-chain variable fragment-derived allergen-specific sequences or IgE sequences of unknown specificity.
The longitudinal tracking of allergen-specific IgE+ clones in patients undergoing SIT revealed their persistence, class switch recombination to IgG subtypes, and unique maturation pattern of a stereotyped Phl p 2 clonotype. The findings provided valuable insights into the mechanisms of desensitization in specific immunotherapy for allergic diseases.