PMID- 34755130
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20220726
IS  - 2666-3791 (Electronic)
IS  - 2666-3791 (Linking)
VI  - 2
IP  - 10
DP  - 2021 Oct 19
TI  - High-resolution epitope mapping by AllerScan reveals relationships between IgE 
      and IgG repertoires during peanut oral immunotherapy.
PG  - 100410
LID - 10.1016/j.xcrm.2021.100410 [doi]
LID - 100410
AB  - Peanut allergy can result in life-threatening reactions and is a major public 
      health concern. Oral immunotherapy (OIT) induces desensitization to food 
      allergens through administration of increasing amounts of allergen. To dissect 
      peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing 
      OIT, we have developed AllerScan, a method that leverages phage-display and 
      next-generation sequencing to identify the epitope targets of peanut-specific 
      antibodies. We observe a striking diversification and boosting of the 
      peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE 
      levels against individual epitopes. High-resolution epitope mapping reveals 
      shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual 
      subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit 
      strikingly similar antibody footprints, suggesting related clonal lineages or 
      convergent evolution of peanut-specific IgE and IgG B cells. Individual 
      differences in epitope recognition identified via AllerScan could inform safer 
      and more effective personalized immunotherapy.
CI  - (c) 2021 The Author(s).
FAU - Chen, Genghao
AU  - Chen G
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
AD  - Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, 
      Brigham and Women's Hospital, Boston, MA 02115, USA.
AD  - Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 
      02115, USA.
FAU - Shrock, Ellen L
AU  - Shrock EL
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
AD  - Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, 
      Brigham and Women's Hospital, Boston, MA 02115, USA.
AD  - Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 
      02115, USA.
FAU - Li, Mamie Z
AU  - Li MZ
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
AD  - Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, 
      Brigham and Women's Hospital, Boston, MA 02115, USA.
FAU - Spergel, Jonathan M
AU  - Spergel JM
AD  - Division of Allergy and Immunology, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
AD  - Department of Pediatrics, Perelman School of Medicine of University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Nadeau, Kari C
AU  - Nadeau KC
AD  - Department of Medicine, Sean N Parker Center for Allergy and Asthma Research, 
      Stanford University, Palo Alto, CA, USA.
FAU - Pongracic, Jacqueline A
AU  - Pongracic JA
AD  - Division of Pediatric Allergy and Immunology, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL 60611, USA.
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
FAU - Umetsu, Dale T
AU  - Umetsu DT
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Rachid, Rima
AU  - Rachid R
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - MacGinnitie, Andrew J
AU  - MacGinnitie AJ
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Phipatanakul, Wanda
AU  - Phipatanakul W
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Schneider, Lynda
AU  - Schneider L
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Oettgen, Hans C
AU  - Oettgen HC
AD  - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, 
      Boston, MA 02115, USA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Elledge, Stephen J
AU  - Elledge SJ
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
AD  - Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, 
      Brigham and Women's Hospital, Boston, MA 02115, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01781637
GR  - R01 AI119918/AI/NIAID NIH HHS/United States
GR  - UL1 TR001422/TR/NCATS NIH HHS/United States
GR  - R01 AI140134/AI/NIAID NIH HHS/United States
GR  - U01 AI126614/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211019
PL  - United States
TA  - Cell Rep Med
JT  - Cell reports. Medicine
JID - 101766894
RN  - 0 (2S Albumins, Plant)
RN  - 0 (Antigens, Plant)
RN  - 0 (Ara h 1 protein, Arachis hypogaea)
RN  - 0 (Ara h 2 allergen, Arachis hypogaea)
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Library)
RN  - 0 (Plant Proteins)
RN  - 0 (Seed Storage Proteins)
RN  - 0 (allergen Ara h3)
RN  - 2P471X1Z11 (Omalizumab)
RN  - 37341-29-0 (Immunoglobulin E)
MH  - 2S Albumins, Plant/administration & dosage/chemistry
MH  - Antigens, Plant/administration & dosage/chemistry
MH  - Arachis/chemistry/immunology
MH  - B-Lymphocytes/immunology/pathology
MH  - Case-Control Studies
MH  - Desensitization, Immunologic/*methods
MH  - Epitope Mapping/*methods
MH  - Epitopes/*chemistry/immunology
MH  - High-Throughput Nucleotide Sequencing
MH  - High-Throughput Screening Assays
MH  - Humans
MH  - Immunoglobulin E/*blood
MH  - Immunoglobulin G/*blood
MH  - Membrane Proteins/administration & dosage/chemistry
MH  - Omalizumab/*therapeutic use
MH  - Peanut Hypersensitivity/genetics/immunology/pathology/*therapy
MH  - Peptide Library
MH  - Plant Proteins/administration & dosage/chemistry
MH  - Precision Medicine
MH  - Seed Storage Proteins
PMC - PMC8563412
OTO - NOTNLM
OT  - IgE
OT  - allergen immunotherapy
OT  - antibody
OT  - antibody repertoire
OT  - epitope mapping
OT  - food allergy
OT  - high-throughput sequencing
OT  - oral immunotherapy
OT  - peanut allergy
OT  - phage display
COIS- S.J.E. is a co-founder of TSCAN Therapeutics, MAZE Therapeutics, ImmuneID, and 
      Mirimus. S.J.E. serves on the Scientific Advisory Board (SAB) of CRISPR 
      Therapeutics; Homology Medicines, Inc.; TSCAN Therapeutics; and X-Chem and is an 
      advisor for MPM. S.J.E. and G.C. have applied for a patent on these findings. 
      J.M.S. has received research funding from Aimmune Therapeutics, Regeneron, 
      Sanofi, Novartis, and FARE. K.C.N. is co-founder of IgGenix, Latitude, Alladapt, 
      and BeforeBrands. She also serves on the SAB or Data and Safety Monitoring Boards 
      (DSMB) of Novartis, Regeneron, ClostraBio, Cour Pharmaceuticals, Aravax, and 
      NHLBI. D.T.U. and H.C.O. serve on the SAB of IgGenix. J.A.P. is on the 
      Independent Data Monitoring Committee of Regeneron and Clinical Advisory Board of 
      FARE and has served as an investigator for Aimmune Therapeutics and FARE. She has 
      received research funding from DBV, FARE, The Sunshine Charitable Foundation, and 
      Peak6 Investments LLC. A.J.M. is an advisor to DBV Technologies. R.R. has 
      received research funding from Aimmune Therapeutics. W.P. is a consultant for 
      Genentech, Novartis, Regeneron, and Sanofi and received research support from 
      Thermo Fisher Scientific. L.S. serves on the Medical Advisory Board for Food 
      Allergy Research and Education and the DSMB for Alladapt and is an investigator 
      for DBV Technologies and Regeneron. None of these affiliations represent a 
      conflict of interest with respect to the design or execution of this study or 
      interpretation of data presented in this manuscript.
EDAT- 2021/11/11 06:00
MHDA- 2021/11/11 06:01
PMCR- 2021/10/19
CRDT- 2021/11/10 06:48
PHST- 2021/02/17 00:00 [received]
PHST- 2021/07/18 00:00 [revised]
PHST- 2021/09/21 00:00 [accepted]
PHST- 2021/11/10 06:48 [entrez]
PHST- 2021/11/11 06:00 [pubmed]
PHST- 2021/11/11 06:01 [medline]
PHST- 2021/10/19 00:00 [pmc-release]
AID - S2666-3791(21)00268-8 [pii]
AID - 100410 [pii]
AID - 10.1016/j.xcrm.2021.100410 [doi]
PST - epublish
SO  - Cell Rep Med. 2021 Oct 19;2(10):100410. doi: 10.1016/j.xcrm.2021.100410. 
      eCollection 2021 Oct 19.