Foodallergy(FA)isapotentiallyfataldisorderinneedofimprovedmethodsfordiagnosis,clinicalmonitoring, andtreatment.Basophils,theleastcommonofthebloodgranulocytes,havebeenimplicatedasimportant contributorstothepathologyofFAandfood-inducedanaphylaxis.Certaincellsurfacephenotypicfeaturescan helptoidentifybasophilswhichhavebeenactivatedbyallergicmechanismsinvivoorinvitro.Inthisproject, wewilldeterminewhetherphenotypicandfunctionalfeaturesofbloodbasophilscanbeusedaspartofan approachtopredicttheseverityofclinicalreactivitytofoodallergensinpeoplewithFAinducedbymultiple foods(herein:multi-FA),toimprovethesafetyandefficacyoforalimmunotherapy(OIT)protocolstotreatFA, and,inprinciple,tocustomizeimmunotherapyprotocolsforeachindividualfoodallergicperson.
In Aim1, wewillperformdetailedimmunophenotypingtomonitorthephenotype(s)andactivationstatusof basophilsandtheirsubpopulationsinthebloodofparticipantswithmulti-FA,asmeasuredexvivoatbaseline (definedhereinaswithoutexvivostimulationwithallergensoranti-IgE).Bloodwillbeobtainedbeforethe patients?enrollmentinapilot,mechanistic-focused,phase2clinicaltrialofmulti-OIT(definedassimultaneous OITwithmultiplefoodallergens)conductedwithorwithoutomalizumabordupilumabandatmultipleintervals duringthecourseofandaftertheendofsuchimmunotherapy(IT)(seeProject1);?wealsowillanalyzeblood frommulti-FAparticipantsnottreatedwithOIT,atopicpeoplewithoutFA,andhealthynon-atopiccontrols.This workwilltestthehypotheses:1)thattheexpressionofactivationand/orothermarkersinbloodbasophilsof multi-FApatientsatbaseline,beforethecells?exvivostimulation,correlateswiththepatients?acuteclinical reactivitytofoodallergensbeforeandduringITandcanbeusedtomonitorthedevelopmentanddurabilityof desensitizationand/orsustainedunresponsiveness/?tolerance?inducedbyIT.
In Aim2, wewillperforminvitrostudiesofbasophilphenotypeandfunction(i.e.,basophilactivationtests [BATs]),tomeasurebasophilresponsestochallengewithfoodallergensexvivo.Thisworkwilltestthe hypothesisthat,inmulti-FApatients,themagnitudeofchangesinbasophilphenotype(e.g.,expressionof activationmarkers)and/orfunction(e.g.,secretionofmediators)inducedbychallengeoftheirbasophilswith foodallergensexvivocorrelateswiththereductioninclinicalevidenceoffoodallergensensitivityduringITand mayalsocorrelatewithclinicaloutcomesofdesensitizationvs.sustainedunresponsiveness/?tolerance?. Oneofourkeylongtermgoalsistodevelopinnovative,rapid,andreliablemethodstomonitorbasophil phenotypeandfunctionthatcanbeusedclinicallyforsuchpurposesaspredictingaperson?sclinicalsensitivity tofoodallergens,predictingtheclinicaloutcomeofOIT,customizingOITandotherITprotocolsforindividual people,and/ormonitoringthedevelopment,effectiveness,ordurabilityofimmunotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI104209-08
Application #
10092913
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2013-07-01
Project End
2024-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
8
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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