title: Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy.
abstract: Specific immunotherapy (SIT) is the only treatment with proved long-term curative potential in patients with allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B-cell repertoires are not well understood.
  
  
  
  We sought to characterize the IgE sequences expressed by allergen-specific B cells and track the fate of these B-cell clones during SIT.
  
  
  
  We used high-throughput antibody gene sequencing and identification of allergen-specific IgE with combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and the nasal mucosa from aeroallergen-sensitized subjects before and during the first year of subcutaneous SIT.
  
  
  
  Of 52 distinct allergen-specific IgE heavy chains from 8 allergic donors, 37 were also detected by using high-throughput antibody gene sequencing of blood samples, nasal mucosal samples, or both. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships.
  
  
  
  In the future, combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies might aid assessment of SIT mechanisms and efficacy.
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Levin
authors.affiliation: Department of Biology, Stanford University, Stanford, Calif; Department of Pathology, Stanford University, Stanford, Calif.
authors.forename: Jasmine J
authors.initials: JJ
authors.lastname: King
authors.affiliation: Department of Immunology, Stanford University, Stanford, Calif.
authors.forename: Jacob
authors.initials: J
authors.lastname: Glanville
authors.affiliation: Department of Pathology, Stanford University, Stanford, Calif.
authors.forename: Katherine J L
authors.initials: KJ
authors.lastname: Jackson
authors.affiliation: Department of Pathology, Stanford University, Stanford, Calif.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Looney
authors.affiliation: Department of Pathology, Stanford University, Stanford, Calif.
authors.forename: Ramona A
authors.initials: RA
authors.lastname: Hoh
authors.affiliation: Center for Molecular Allergology, IDI-IRCCS, Rome, Italy; Associated Centers for Molecular Allergology, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Mari
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Skåne University Hospital, Lund, Sweden.
authors.forename: Morgan
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Skåne University Hospital, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Greiff
authors.affiliation: Department of Pathology, Stanford University, Stanford, Calif; Department of Genetics, Stanford University, Stanford, Calif.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
authors.affiliation: Department of Pathology, Stanford University, Stanford, Calif.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden. Electronic address: mats.ohlin@immun.lth.se.
authors.forename: Mats
authors.initials: M
authors.lastname: Ohlin
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003888:Desensitization, Immunologic; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D055815:Young Adult
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E
keywords: Aeroallergens; IgE; allergen-specific antibodies; clonotype evolution; immunoglobulin class-switch; local immunity; repertoire; specific immunotherapy