Role of Memory IgG B Cells in the Development of Tolerance in Food Allergy
Role of Memory IgG B Cells in the Development of Tolerance in Food Allergy
批准号:
10377446
负责人:
Sarita U Patil
金额:
$25.2万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-03-24 至 2023-02-28
关键词:
AddressAffectAffinityAllergensAllergicAllergic DiseaseAllergy to peanutsAntibodiesAntibody RepertoireAntigensB-LymphocytesB-cell receptor repertoire sequencingBasophilsBiological AssayBiological MarkersCellsClinicalClinical TrialsClonal EvolutionClonalityDevelopmentEpitopesEvolutionFood HypersensitivityFrequenciesHumanHumoral ImmunitiesIgEImmune ToleranceImmunoglobulin AImmunoglobulin Class SwitchingImmunoglobulin GImmunoglobulin Switch RecombinationImmunotherapyLeadLibrariesLifeLinkMass Spectrum AnalysisMeasuresMediatingMemoryMemory B-LymphocyteModalityOral CharactersOutcomePathogenicityPatientsPopulationPositioning AttributePrevalenceProcessProteomicsPublic HealthPublishingReactionRecombinant AntibodyRiskRoleSerumSpecificitySurfaceTechniquesTestingTimeTreatment Efficacybaseclinical efficacydeep sequencingearly detection biomarkersfood allergennovel therapeutic interventionnovel therapeuticsoral immunotherapypatient subsetspreventtechnique developmenttooltreatment strategy
中文摘要
只有一小部分ige介导的食物过敏患者在口服后出现临床耐受性
英文摘要
Only a subset of patients with IgE-mediated food allergy develop clinical tolerance after oral
immunotherapy (OIT), which has been attributed to the development of protective, functionally suppressive
antibodies. However, those who lose tolerance are often seen to have an early transient increase in allergen-
specific IgE. Previously, we have described the induction of allergen-specific memory B cells early in OIT, and
these specific IgG B cells could serve as a reservoir of IgE memory via sequential class-switching. Therefore,
the relative contribution of specific IgG B cells giving rise to protective IgG or IgA antibodies versus pathogenic
IgE is critical to the development of immunological tolerance in OIT. Understanding the contributions of that B
cell fate decision could lead to the development of new therapeutic modalities for allergic diseases.
In OIT, we recently published that suppression of basophil sensitivity is a biomarker of tolerance.
Functional suppression of basophils and not bulk levels of allergen-specific IgG is correlated with tolerance,
suggesting that the antibody repertoire induced by OIT may be highly relevant to the development of tolerance.
We have developed a highly specific fluorescent multimer to identify and characterize allergen-specific B cells
in peanut OIT in order to define the clonal contributions of these B cells. Using these tools, we propose to track
clonal evolution from the memory IgG B cells induced by OIT to the post-serum effector antibodies to explain
how antibody evolution from specific IgG B cells influences clinical outcomes in OIT.
Based on these findings, we hypothesize that allergen-specific memory IgG B cells can give rise to
either protective or pathogenic antibodies that determine long-lived tolerance after OIT. Our approach
combines the isolation of antigen-specific B cells for single-cell BCR sequencing, BCR repertoire analysis, and
serum proteomics to dissect the clonality of serum antibodies to the peanut allergen, Ara h 2, over the course
of OIT. We are uniquely positioned to conduct this study in that we have both serum and BCR repertoires from
previously characterized OIT-treated patients. We will address our hypothesis in the following specific aims: (1)
Evaluate the development of protective, functionally suppressive allergen-specific IgG in sustained tolerance
after OIT; and (2) Evaluate the role of sequential switching in the loss of tolerance after OIT.
We anticipate that the proposed studies will elucidate the connection between long-lasting clinical
efficacy of OIT on a clonal level with protective and pathogenic antibodies, highlighting the critical role of
memory allergen-specific IgG B cells and leading to new strategies for the treatment of food allergies. The
development of techniques to track antigen-specific B cell fate, using BCR sequencing, proteomics and
recombinant antibodies, will provide a powerful platform to further refine our understanding of how humoral
immunity drives allergic disease in humans.
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EAACI task force report: A consensus protocol for the basophil activation test for collaboration and external quality assurance.
EAACI 工作组报告:用于协作和外部质量保证的嗜碱性粒细胞激活测试的共识协议。
DOI:
10.1111/all.15907
发表时间:
2024
期刊:
Allergy
影响因子:
12.4
作者:
[Pascal,M, Edelman,SM, Nopp,A, Möbs,C, Geilenkeuser,WJ, Knol,EF, Ebo,DG, Mertens,C, Shamji,MH, Santos,AF, Patil,S, Eberlein,B, Mayorga,C, Hoffmann,HJ]
通讯作者:
Hoffmann,HJ
DOI:
10.1016/j.jaci.2021.12.796
发表时间:
2022-07
期刊:
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
影响因子:
14.2
作者:
[Hazebrouck, Stephane, Patil, Sarita U., Guillon, Blanche, Lahood, Nicole, Dreskin, Stephen C., Adel-Patient, Karine, Bernard, Herve]
通讯作者:
Bernard, Herve
DOI:
10.1172/jci164501
发表时间:
2023-01-17
期刊:
JOURNAL OF CLINICAL INVESTIGATION
影响因子:
15.9
作者:
[LaHood, Nicole A., Min, Jungki, Keswani, Tarun, Richardson, Crystal M., Amoako, Kwasi, Zhou, Jingjia, Marini-Rapoport, Orlee, Bernard, Herve, Hazebrouck, Stephane, Shreffler, Wayne G., Love, J. Christopher, Pomes, Anna, Pedersen, Lars C., Mueller, Geoffrey A., Patil, Sarita U.]
通讯作者:
Patil, Sarita U.
DOI:
10.1097/aci.0000000000000774
发表时间:
2021-10-01
期刊:
Current opinion in allergy and clinical immunology
影响因子:
2.8
作者:
[Keswani T, Patil SU]
通讯作者:
Patil SU
Role of Memory IgG B Cells in the Development of Tolerance in Food Allergy
-
批准号:10196244
-
项目类别:
-
资助金额:$21.0万
-
财政年份:2021
-
负责人:Sarita U Patil
-
依托单位:
Structural and functional characterization of protective antibodies induced in peanut oral immunotherapy
-
批准号:10306372
-
项目类别:
-
资助金额:$50.26万
-
财政年份:2020
-
负责人:Sarita U Patil
-
依托单位:
Structural and functional characterization of protective antibodies induced in peanut oral immunotherapy
-
批准号:10507767
-
项目类别:
-
资助金额:$50.26万
-
财政年份:2020
-
负责人:Sarita U Patil
-
依托单位:
Humoral mechanisms of tolerance in peanut oral immunotherapy
-
批准号:9013624
-
项目类别:
-
资助金额:$18.62万
-
财政年份:2016
-
负责人:Sarita U Patil
-
依托单位:
The Role of Basophils in Adaptive Immunity
-
批准号:8650653
-
项目类别:
-
资助金额:$6.31万
-
财政年份:2013
-
负责人:Sarita U Patil
-
依托单位:
The Role of Basophils in Adaptive Immunity
-
批准号:8456533
-
项目类别:
-
资助金额:$5.94万
-
财政年份:2013
-
负责人:Sarita U Patil
-
依托单位:
海外基金