Peptide immunotherapy for childhood allergy - addressing translational challenges 英文参考文献.docVIP

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Peptide immunotherapy for childhood allergy - addressing translational challenges 英文参考文献.doc

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Peptide immunotherapy for childhood allergy - addressing translational challenges 英文参考文献

Mackenzieetal.ClinicalandTranslationalAllergy2011,1:13 /content/1/1/13 REVIEW OpenAccess Peptideimmunotherapyforchildhood allergy-addressingtranslationalchallenges KarenJMackenzie1,2,StephenMAnderton1,3 andJürgenSchwarze1,2* Abstract Allergicsensitisationusuallybeginsearlyinlife.Thenumberofallergensapatientissensitisedtocanincreaseover timeandthedevelopmentofadditionalallergicconditionsisincreasinglyrecognised.Targetingallergicdiseasein childhoodisthuslikelytobethemostefficaciousmeansofreducingtheoverallburdenofallergicdisease.Specific immunotherapyinvolvesadministeringproteinallergentotoleriseallergenreactiveCD4+Tcells,thoughtkeyin drivingallergicresponses.Yetspecificimmunotherapyrisksallergicreactionsincludinganaphylaxisasa consequenceofpreformedallergen-specificIgEantibodiesbindingtotheprotein,subsequentcross-linkingand mastcelldegranulation.CD4+Tcellsdirecttheirresponsestoshort“immunodominant”peptideswithinthe allergen.SuchpeptidescanbegiventherapeuticallytoinduceTcelltolerancewithoutfacilitatingIgEcross-linking. Peptideimmunotherapy(PIT)offersattractivetreatmentpotentialforallergicdisease.However,PIThasnotyet beenshowntobeeffectiveinchildren.ThisreviewdiscussestheimmunologicalmechanismsimplicatedinPITand brieflycoversoutcomesfromadultPITtrials.Thisprovidesacontextfordiscussionofthechallengesforthe applicationofPIT,bothgenerallyandmorespecificallyinrelationtochildren. Keywords:Allergy,Children,PeptideImmunotherapy Introduction andmodifyingdiseaseprogressionisthereforeahugely Allergicdiseaseincludingatopiceczema,allergicrhinitis, attractivetherapeuticgoal[10]. allergic asthma and food allergy causes significant EvidencesuggestsakeyroleforCD4+Tcells,particu- patientmorbidityandeconomiccoststohealthcaresys- larly the T helper (Th) 2 subset, in allergy. These cells tems[1,2].Currentclinicalmanagementprimarilyrelies express thetranscription factor GATA-binding protein on allergen avoidance, treating symptoms as they arise 3 (GATA-3) and can produc