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Clonal evolution an...
Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy
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- Hoh, Ramona A. (author)
- Stanford University School of Medicine
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- Thörnqvist, Linnea (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Yang, Fan (author)
- Stanford University School of Medicine
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Godzwon, Magdalena (author)
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- King, Jasmine J. (author)
- Stanford University School of Medicine
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- Lee, Ji Yeun (author)
- Stanford University School of Medicine
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- Greiff, Lennart (author)
- Lund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Vårdrelaterade infektioner hos svårt och kristiskt sjuka,Forskargrupper vid Lunds universitet,Huvud- och halscancergruppen,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Health care related infections in seriously and critically ill patients,Lund University Research Groups,Head and Neck Cancer Research Group,Skåne University Hospital
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- Boyd, Scott D. (author)
- Stanford University School of Medicine
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- Ohlin, Mats (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English 16 s.
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 152:1, s. 214-229
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- Aeroallergens
- allergen-specific antibodies
- clonotype evolution
- IgE
- IgG
- immunoglobulin repertoire
- isotype class switch
- local immunity
- specific immunotherapy
- stereotyped immunoglobulin rearrangement
Publication and Content Type
- art (subject category)
- ref (subject category)
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