ORAL ABSTRACT SESSIONS FOOD ALLERGY

335 Pages·2013·4.4 MB·English

ABSTRACTS
TM
Abstracts of the XX World Allergy Congress 2007
December 2–6, 2007, Bangkok, Thailand
ORAL ABSTRACT SESSIONS Methods:In-vitroheatstabilityoftheproteinwasassessed.Cholineoxidase
FOOD ALLERGY inducedallergenicitywasassessedinBalb/cmice.IgEreactivityofcholine
oxidase protein was assessed with atopic patients` sera. Acute toxicity of
cholineoxidaseproteinwasalsoassessedinmicemodel.
Results:Cholineoxidaseproteinwasstableat90-Cfor1hourandreacted
1
withcholineoxidaseantibodiesonimmunoblot.SpecificIgElevelswerelow
IL-10genepolymorphism,butnotTGF-"1genepolymorphisms,
incholineoxidasetreatedmicecomparabletocontrol,whileOVAsensitized
isassociatedwithfoodallergy in a Japanese population
miceshowedhighIgElevels.Intravenouschallengewithcholineoxidasedid
Eduardo Campos1, Naoki Shimojo1, Yoichi Suzuki2, Takayasu Arima1, not induce any adverse reaction but i.v challenge with OVA led to
Tomoko Matsuura1, Yuzaburo Inoue1, Akiko Yamaide3, Seiko Tokita1, anaphylaxis in OVA sensitized mice. Choline oxidase sensitized mice
Minako Tomiita1, Katsunori Fujii1, and Yoichi Kohno1. 1Chiba University, demonstrated IL-4 release similar to control in splenic culture supernatant
Pediatrics, Chiba, Japan; 2Chiba University, Public Health, Chiba, Japan; however, OVA sensitized mice showed higher IL-4 levels. Histological
3ChibaChildren’sHospital,Pediatrics,Chiba,Japan. analysisoflungtissuesfromcholineoxidasesensitizedmiceshowedintact
Background: The regulatory IL-10 and TGF-$1 cytokine gene polymor- epithelium with normal airways, whereas OVA sensitized mice showed
phismshavebeenassociatedwithallergicdiseasesindifferentpopulations, narrowing of airways with increased eosinophilic infiltration. ELISAwith
likeCaucasian,ChineseandIndians.However,noassociationsbetweenIL-10 allergic patients` sera (n=45) revealed low specific IgE binding (mean OD
andTGF-$1genepolymorphismsandfoodallergy(FA)inJapanesechildren 0.281) with choline oxidase protein. Acute toxicity studies of choline
have been evaluated so far. To clarify the relationship of polymorphisms oxidase protein in mice model showed no significant difference (p90.05)
ofthese2regulatorycytokinegeneswithFA,notatopyitself,polymorphisms with control in growth, body weight, food consumption and blood
IL-10AV1082G,CV819TandTGF-$1T+869C,G+915C,CV509TinFA biochemicalindices.Histopathologyofguttissuesofmicefedwithcholine
patientswerecomparedwiththoseinnon-FAatopiccontrols. oxidase showed normal gastric mucosa lining with normal villi in jejunum
Methods: One hundred-eleven childhood FA patients, with a mean andileumsections.
7.6T4.0 years of age and 115 atopic control children without FA (mean = Conclusion:Bacterialcholineoxidaseproteinisheatstablebutfailedtoelicit
8.2T1.5yearsofage)wererecruited.MostofFApatientsandatopiccontrols allergicresponseinmicemodel.Thesedataindicatescholineoxidaseprotein
were sensitized with house dust mite (92% and 93%, respectively). DNA maybesafeforuseintransgeniccrops.
samplesfromthesesubjectsweregenotypedbyusingRealTimePCR.
Results:Theoddsratio(OR)ofIL-10V1082AAgenotypewas2.5(95%CI,
1.0Y6.4)for food allergy risk when compared with atopic control subjects
(p = 0.03). This study had a power of 80% to achieve significance at the
4
0.05levelforIL-10V1082AallelewhenORisgreaterthan2.3.OurORvalue
Identification ofaminoacids criticalforIgE-binding to
was2.4;therefore,weconsiderthisassociationhadenoughstatisticalpower sequentialepitopesofbovine0-caseinandthesimilarityofthese
tosupportourfinding.Therewerenosignificativedifferencesinthefrequency epitopesto the corresponding human 0-caseinsequence
ofIL-10CV819TandTGF-$1genepolymorphismsbetweenbothgroups.
Conclusion:ThisresultindicatesthatIL-10AV1082Ggenepolymorphism Kirsi M.Jarvinen, NancyHan, RenataR. Cocco,Paula J. Busse,Hugh A.
Sampson, and Kirsten Beyer. Mount Sinai School of Medicine, Division of
isassociatedwithfoodallergysusceptibilityinatopicJapanesechildren.Our
PediatricAllergyandImmunology,NewYork,UnitedStates.
findings should encourage further studies to elucidate the functional
relationshipofIL-10AV1082GgenepolymorphisminFApathogenesis. Background: The delineation of allergenic (i.e. IgE-binding) epitopes in
cow`s milk proteins and the amino acids [AAs] critical for IgE binding is
necessarytobetterunderstandthestructuralpropertiesofanallergenandto
develop more efficacious immunotherapeutic reagents. Furthermore, this
2 Abstract withdrawn information may enable us to better understand cross-sensitivity between
differentallergens.
Methods: Eleven peptides, 10 to 14 AAs in length, representing the IgE-
3 binding epitopes of 0-casein were synthesized on a derivatized cellulose
Safetyassessmentofbacterialcholineoxidaseproteinintroduced membranewith single AA substitutions at each position. Membranes were
in transgenic crops incubatedwithpooledserafrom15milk-allergicpatientsandindividualsera
AbinavKumarSingh1,BhanuPratapSingh1,GBKSPrasad2,ShailendraNath fromtenofthepatientsincludedinthepool.
Gaur3, and Naveen Arora1. 1Institute of Genomicsand Integrative Biology, Results:For 10 of the 11 allergenic peptides, one to five different single
AllergyandImmunologyDepartment,Delhi,India;2JiwajiUniversity,SOS, AA substitutions resulted in elimination of IgE-binding of pooled patient
Department ofBiotechnology,Gwalior,India;3V.P.ChestInstitute,Depart- sera. Overall at least one mutated peptide could be found for these 10
mentofRespiratorymedicine,Delhi,India. IgE-binding sites that resulted in a reduction of IgE binding in at least
Background: Previously, transgenic Brassica juncea expressing bacterial 80% of the patients who recognized the native protein. Furthermore, the
cholineoxidaseproteindidnotshowenhancedallergenicityasevaluatedby IgE-binding region at AA104-112 on bovine 0-casein showed a high
WHO/FAOguidelines.Inthepresentstudy,cholineoxidaseproteinderived degree of similarity with the human 0- casein, respectively, including the
fromArthrobacterglobiformiswasassessedforallergenicityandtoxicity. AAs critical for IgE binding.
World AllergyOrganization Journal & November 2007 S1
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Abstracts World AllergyOrganization Journal & November 2007
Conclusion:ThisdatasuggeststhatcriticalAAsshouldbeassessedwithboth peanutallergicpatientsusingWesternblotanalysis.Skinpricktest(SPT)were
pooled and individual patient sera to account for the B-cell epitope alsoperformedon5peanutallergicpatientsusingrawandlightroastpeanuts.
heterogeneity between patients with cow`s milk allergy. In addition, we Results:WefoundthatwhilethesecondarystructureofArah2fromraw,LR
identifiedtwopotentiallycross-reactivepeptidesbetweenbovineandhuman andDRpeanutislargelyaffectedwithadditionofdi-thoithreatol(DTT),the
caseinsofunknownclinicalrelevance. roasting process itself only slightly altered the secondary structure and
solubility,whilerenderingArah2muchmoreresistanttodigestion.Minor
changeswereseeninthesecondarystructureofArah1fromraw,LRandDR
peanutwiththeadditionofDTT,buttheproteinbecamelesssolubleandmore
5 resistant to digestion (with changes in the size and number of digestion
Foodallergenabsorptionkineticsandgastricdigestioninfluence resistantfragments)withthedegreeofroasting.TheSPTreactivitytoroasted
clinicalreactivity in allergic patients peanutwaseitherequal(2/5)orstronger(3/5)thantorawpeanut.
EvaUntersmayr1,HelleVestergaard2,Hans-JorgenMalling2,LouiseBjerremann Conclusion:ThealterationsinIgEbindingandresistancetodigestionofthe
Jensen3, Michael H. Platzer3, George Boltz-Nitulescu1, Otto Scheiner1, peanutproteinsismostlikelyduetochemicalmodificationsand,minutely,ifat
Per Stahl Skov3, Erika Jensen-Jarolim1, and Lars K. Poulsen2. 1Medical all,tosmallstructuralchanges.Aspreviouslysuggested,theMaillardreaction
UniversityVienna,DepartmentofPathophysiology,Vienna,Austria;2National is most likely the predominant contributor to the decreased solubility and
digestibilityoftheproteinsinroastedpeanuts.Thisimpliesthatpatientswith
University Hospital Copenhagen, Laboratory for Medical Allergology,
Copenhagen,Denmark;3NationalUniversityHospitalCopenhagen,Labora- higherskintestreactivitytotheroastedpeanuthavespecificIgEtoepitopes
thatarechemicallymodifiedbytheroastingprocessratherthantostructurally
toryforMedicalAllergology,ReferenceLab,Copenhagen,Denmark.
alteredepitopesinadditiontootherIgEepitopesthatarerecognizedbythe
Background: Severeallergicreactionstominuteamountsof ingestedfood
majorityofpeanutallergicpatients.
proteinsrepresentmajorproblemsforboth,theallergicpatientsandthefood
industry. Even though protein absorption pattern and physiological protein
degradationmightsubstantiallyinfluenceclinicalreactivityinallergicpatients
INFLAMMATORY MECHANISMS
onlylimitedknowledgeisavailabletodate.Thus,inthepresentstudyweused
fishasamodelantigenaimingtoanalyzeproteinuptakeandtheroleofgastric
digestioninfishallergy.
Methods and Results: Open challenges of healthy subjects with fish 7
followedbyproteindeterminationinbloodsamplesrevealedtheabsorption Transferof exosomes between human mast cells
of biologically active fish proteins within 10 minutes after ingestion. Even KarinEkstro¨m,HadiValadi,MargaretaSjo¨strand,andJanLo¨tvall.Institution
thoughmaximalserumlevelsweremeasuredafter1Y2h,apartialpregastric ofMedicine,SahlgrenskaAcademy,Go¨teborgUniversity,Go¨teborg,Sweden.
absorption was indicated. Additionally, simulated gastric fluidexperiments, Background: Exosomes are 30 to 90 nm membranevesicles of endocytic
RASTinhibitionassay,histaminereleaseandskintestingwithfishproteins originreleasedbymanydifferentcellsincludingdendriticcells,lymphocytes,
determinedphysiologicalgastricdigestiontoreducetheallergicpotentialof epithelialcellsandmastcells.Thefunctionofexosomesisnotfullyknown,
fish up to 10,000-fold, which was evidenced also by significantly smaller buttheyarebelievedtotakepartincommunicationbetweencells.Theaimof
wheal reactions in skin tests. However, protein digestion was abrogated thisstudywastoexaminethetransferofexosomesbetweenhumanmastcells.
when digestion experiments were repeated imitating hypoacidic conditions Mastcellderivedexosomeshavepreviouslybeenshowntocontainaselection
ingastricfluids.FishdigestedatpHof2.75andaboverevealedcomparable ofmRNAandmiRNAinadditiontoproteins.
reactivity patterns as undigested extracts. Moreover, these test materials Methods: Exosomes released from the human mast cell line HMC-1 were
triggered severe clinical reactions at 10- to 30-fold lower cumulated isolated by repeated centrifugations and filtrations steps. Exosomes were
challenge doses in fish allergic patients in blinded challenges. detected using electron microscopy and flow cytometry. For flow cytometric
Conclusion: Ourdataclearlyunderlinetheparamountclinicalrelevanceof analysis, exosomes were conjugated to anti-CD63 latex beads and immuno-
gastric digestion in fish allergy. Therefore, insufficient gastric digestion stainedagainstthetetraspaninsCD9,CD63andCD81withPElabelledanti-
represents a risk factor for fish allergic patients to develop anaphylactic bodies.ExosomeswerelabelledwiththegreenfluorescentstainPKH67,washed
reactionsatsignificantlyloweredallergenthresholdlevels. andco-culturedwithHMC-1cells.Thecellswereharvestedafter0,3and5h,
washed,fixedinformaldehydeandexaminedbyflowcytometricanalysisandby
fluorescencemicroscopy.Resultsarepresented as %positivecells and mean
fluorescenceintensity(MFI)fromtwoindependentexperiments(n=4).
6 Results: HMC-1 exosomes were identified by electron microscopy and by
Structural,chemicalandimmunogeniceffectsofroastingpeanut flowcytometricanalysis.Theseexosomeswerepositiveforthetetraspanins
SoheilaMaleki1,SamiBahna2,andBrianWilson2.1USDeptofAgriculture, CD9, CD63 and CD81and could be transferred to HMC-1 cells. After 3h
FoodAllergyResearchUnitq,NewOrleans,UnitedStates;2LouisianaState incubation,54%oftheHMC-1cellswerepositiveforPKH67(MFI243)and
after5h71%ofthecellswerepositive(MFI332)comparedtothenegative
UniversityHealthSciencesCenter,Allergy&Immunology Section,Shreve-
control.
port,UnitedStates.
Conclusion:Theresultsdemonstratethathumanmastcellsreleaseexosomes
Background: In previous studies, we have shown that processes such as
that can be transferred to other human mast cells. This exosome-mediated
roasting,canalter theallergenicpropertiesofpeanuts.Tounderstandthese
communicationbetweenmastcellsmaybeimportantinallergicdiseases.
observationsatamolecularlevel,thesolubility,digestibility,IgEbidingand
structuralcharacteristicsofArah1andArah2purifiedfromrawandroasted
peanutswereassessed.Also,skinpricktestanalysiswasperformedwithraw
androastedpeanutstodeterminealteredimmunogenicity.
Methods:ThesolubilityanddigestibilityofArah1andArah2withinthe 8
contextofpeanutsroastedtodifferentdegreeswereassessedusingSDS-PAGE Interferon-$ augmentseosinophil adhesion-inducingactivityof
andallergenspecificantibodies.Arah1andArahpurifiedfromraw,light endothelial cells
roast(LR)anddarkroast(DR)peanutsweresubjectedtocirculardichroism MakotoNagata,TakehitoKobayashi,YotaroTakaku,KoichiHagiwara,and
spectroscopy before and after reduction of disulfide bonds, digestion with Minoru Kanazawa. Saitama Medical University, Respiratory Medicine,
trypsinandpepsinfollowedbySDS-PAGE,andIgEbindingwithserafrom Moroyama-machi,Iruma-gun,Saitama,Japan.
S2 *2007World Allergy Organization
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World AllergyOrganization Journal & November 2007 Abstracts
Background: Viral infections induce exacerbations of asthma. One of the
earliesthostresponsestoviralinfectionsistheproductionofinnatecytokines 11
includingtypeIinterferons(IFNs),suchasIFN-$,whichmayacttomodify Theinfluenceofmaternalallergyonp38-MAPKinaseactivityin
airwayinflammation.Theobjectiveofthisstudywastoinvestigatewhether CD14+monocytes from 2-and 5-yearoldchildrenfollowing
IFN-$modifiestheeosinophiladhesion-inducingactivityofendothelialcells. microbial challenge
Methods:Humanumbilicalveinendothelialcells(HUVECs)werestimulated Shanie Saghafian-Hedengren1, Petra Amoudruz1, Ulrika Holmlund1, Caro-
withIFN-$for24hinthepresenceorabsenceofTNF-".Eosinophilswere lineNilsson2,andEvaSverremark-Ekstro¨m1.1Wenner-Greninstitute,Dep.of
isolatedfrom the peripheral bloodof healthy volunteers. The abilityof the Immunology, Stockholm University, Sweden; 2Sachs Children’s Hospital,
IFN-$-stimulated HUVEC monolayers to induce eosinophil adhesion was DepartmentofPediatrics,Stockholm,Sweden.
assessedaccordingtotheeosinophilperoxidaseassay. Background: Monocytesaremembersofthe innatebranchofthe immune
Results: Eosinophil adhesion to HUVECs was significantly augmented systemandexpressawiderangeofdifferentpattern-recognitionreceptorscalled
byIFN-$notintheabsencebutinthepresenceofTNF-".Theaugmented toll-likereceptors(TLRs)thatrecognizeconservedpathogenderivedmotifs.
adhesion was inhibited by anti-"4 integrin monoclonal antibody (mAb) TLR-mediatedsignalling,whichinvolvesp-38mitogenactivatedproteinkinase
or anti-$2 integrin mAb. IFN-$ significantly enhanced the expression of (MAPK)activation,ultimatelybridgesinnate-toadaptiveimmuneresponses.
VCAM-1andICAM-1onHUVECsinthepresenceofTNF-". Weshowedpreviouslythatcordbloodmononuclearcellsfromneonateswith
Conclusion: IFN-$ can augment the adhesiveness of endothelial cells to maternalallergyhaddecreasedIL-6levelsuponchallengewiththebacterial
eosinophils,mainlythroughtheexpressionsofVCAM-1andICAM-1.This componentandTLR-ligandpeptidoglycan(PGN),suggestingthatthemonocyte
actionofIFN-$maycontributetotheintensificationofairwayinflammationin populationinchildrenofallergicmothershasanaltered microbialresponse
asthmathatisassociatedwithexacerbationsinducedbyviralinfections. alreadyatbirth.Itispossiblethatsuchalterationpersistsduringchildhood.
Objective: Toexaminemonocyticmicrobialresponseswithregardstop-38
MAPKactivationinCD14+cellsandtomeasureIL-6releasefrommono-
nuclearcellsin2-and5-yearoldchildren.
9 Abstract withdrawn
Methods:The2-and5-yearoldsubjects(n=61total)weregroupedbasedon
having or not having allergic mothers. Peripheral blood mononuclear cells
(PBMCs)fromthechildrenwerestimulatedeitherwithmedium,LPSorPGN
10
invitro.CD14+monocyteswereanalyzedforp-38MAPKactivitybyFACS
CXCand CCchemokines producedbyhuman
andIL-6releasefromPBMCcultureswerequantifiedbyeitherCBAorELISA.
respiratoryepithelium
Results: PBMCs from 2-year old children with allergic mothers release
Ilja Striz1, Eliska Krasna1, Libor Kolesar1, Antonij Slavcev1, Marcela
significantlyless(pG0.05)IL-6uponPGNstimulicomparedtoagematched
Jaresova1, and Jaromir Musil2. 1Institute for Clinical and Experimental
infantswithnon-allergicmothers.2-yearoldinfantswithallergicmothersalso
Medicine,DepartmentofImmunology,Prague,CzechRepublic;2University
display markedly reduced CD14+ monocyte p38-MAPK phosphorylation
HospitalMotol,PulmonaryDepartment,Prague,CzechRepublic.
after LPS (pG0.05) and PGN (pG0.01) challenge. This altered microbial
: Chemokinesregulateleukocytetraffickingduringtheirphysiological
response was attributed to maternal allergy rather than to being IgE-
turnover and recruitment to mucosal surfaces in inflammatory reactions.
sensitizedat2-yearsofage.Attheageof5however,thesedifferencescouldnot
Respiratory epithelium with the ability to respond to locally generated
beseenbetweenthegroupsonthebasisofmaternalallergy.However,children
cytokinesmightbeanimportantsourceofchemokinesattractingdiversecell
with a developed IgE-mediated allergy tended to have higher levels of
populations. With this respect, the aim of our study was to compare the
phosphorylated p38-MAPKupon challengewith LPS and PGN. Theyalso
capacity of different proinflammatory cytokines to stimulate the gene
showedsignificantlyincreasedbasallevelsofIL-6intheculturesupernatants.
expression,productionandreleaseofmultipleCCandCXCchemokinesby
Conclusion: Maternal allergy renders the monocytic population less
respiratoryepithelialcellline.Thechemokinedistributionwasstudiedalsoin
responsivetomicrobialchallengeto(atleast)theageof2whilethisinfluence
bronchoalveolarlavagefluid(BAL)andexhaledbreathcondensates(EBC)of
isnotnotedattheageof5.However,5-yearoldinfantswithIgE-mediated
patientsundergoinglungtransplantation.
allergytendedtohavehigherinflammatoryactivitybothatbasalIL-6levelsas
A total of 96 chemokines and chemokine receptor genes has been
wellasuponchallengewithbacterialcomponents.
studied using an oligoarray system (Superarray Inc.) in cultured human
alveolartype-IIlikecellsA549stimulatedbymultipleconcentrationsofTNF
alpha, IFN gamma, IL-1 beta, IL-18, and IL-33. The chemokine levels in
culture supernatants, BAL, and EBC were measured using multiplex 12Abstract withdrawn
immunoluminometricassay(Luminex)orbyELISA.
In repetitive experiments, epithelial cells constitutively expressed
mRNAforCXCL1(Gro-alpha),CXCL2(Gro-beta),CXCL3(Gro-gamma),
CXCL5 (ENA-78), CXCL6 (GCP-2), and CXCL8 (IL-8), chemokines
attractingpreferentiallyneutrophils.CellsstimulatedwithIL-1betaorTNF
alphaupregulatedmRNAexpressionofchemokinesspecificformononuclear
cells recruitment such as CCL2 (MCP-1), CCL4 (MIP 1 beta), CCL5
(RANTES),andCCL20(MIP3alpha).FortheinductionofofCXCL10(IP-
10)andCXCL11(I-TAC)whichattractactivatedTlymphocytes,IFNgamma
was the most potent stimulus. The induction of epithelial cells by IL-1
relatedcytokines,IL-33andIL-18,resultedonlyinamoderateupregulation
of few CC or CXC chemokines compared to a potent effect of IL-1 beta
stimulation. Epithelium derived chemokines such as CXCL5, CXCL8,
CCL2, CCL4 or CCL5 are abundant in BAL fluids but can be only rarely
detectedinEBC.Weconcludefromourdatathatrespiratoryepithelialcells
are involved in regulating the influx of different populations of inflamma-
tory cells by release of multiple CC and CXC chemokines in a highly
coordinated manner.
*2007WorldAllergyOrganization S3
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Abstracts World AllergyOrganization Journal & November 2007
Foxp3-CD4+ lymphocyte numbers andtotal serum
IgEin early childhood
L.KeokiWilliams1,JenniferOliver2,EdwardL.Peterson2,KevinR.Bobbit2,
Michael J. McCabe Jr.3, Derek Smolarek2, Suzanne L. Havstad2, Ganesa
Wegienka2,GanesaWegienka2,EstebanG.Burchard4,DennisR.Ownby5,and
Christine C. Johnson2. 1Henry Ford Hospital, Internal Medicine, Detroit,
Michigan, United States; 2Henry Ford Hospital,Biostatistics and Research
Epidemiology, Detroit, Michigan, United States; 3University of Rochester
School of Medicine, Environmental Medicine, Rochester, New York, United
States; 4University of Californial San Francisco, Internal Medicine, San
Francisco,California,UnitedStates;5MedicalCollegeofGeorgia,Pediatrics,
Augusta,Georgia,UnitedStates.
Background: Innate immunesystem stimuli, suchas endotoxin, appear to
influenceallergyrisk.Previouslywedescribedgene-environmentinteraction
betweenanendotoxinreceptorpolymorphism,CD14C-260T,andendotoxin
exposure on total serum IgE; however, the mechanism of this interaction
is not known. The objective of this study was to examine whether this
EPIDEMIOLOGY gene-environment interaction influences early CD4+Foxp3- and CD4+
Foxp3+ lymphocyte numbers.
Methods: Participating children were part of a birth cohort in the Detroit,
metropolitanarea.Participantsweregenotypedfor theCD14C-260Tpoly-
13
morphism.Endotoxinexposurewasestimatedfromdustmeasuredinthehome
Prenatalexposureto household petsinfluences fetal
whenchildrenwereage6months.IntracellularFoxp3proteinexpression,a
immunoglobulin Eproduction
regulatory T-cell (Treg-cell) marker, was used to characterize CD4+ lym-
Christine C. Johnson1, Niladri Aichbhaumik2, Ronald Strickler3, Ganesa
phocytesinbloodcollectedatage12months;totalserumIgEwasalsomea-
Wegienka1,DennisR.Ownby4,SuzanneL.Havstad1,andEdwardZoratti2.
sured at this time. Since race-ethnicity may confound or modify genetic
1HenryFordHospital,Biostatistics&ResearchEpidemiology,Detroit,United
associations,westratifiedallanalysesbyrace-ethnicity.
States;2HenryFordHospital,Medicine,Detroit,UnitedStates;3HenryFord
Results: We observed a significant gene-environment interaction between
Hospital,Obstetrics&Gynecology,Detroit,UnitedStates;4MedicalCollege
CD14C-260TgenotypeandendotoxinexposureonCD4+lymphocytenum-
ofGeorgia,Pediatrics,Augusta,UnitedStates.
bers, particularly CD4+Foxp3- lymphocytes. Stratified analyses suggested
Background:Earlylifepetexposuremayprotectagainstallergicsensitization
effectmodification byrace-ethnicityonCD4+Foxp3+ lymphocyte numbers
duringchildhood.Few studieshaveevaluatedthe effectof prenatalpetex-
withasignificantinteractioninAfrican-Americanchildrenbutnotinwhite
posureonpotentialneonatalmarkersofallergicrisk.Weinvestigatedwhether
children. The interaction between CD14 C-260T genotype and endotoxin
maternalexposuretopetsaffectscordbloodIgElevelsinapopulation-based,
exposureontotalIgElevelswasoppositethatobservedforCD4+lymphocyte
generalrisk,ethnicallymixedbirthcohort.
numbers,suggestingreciprocalrelationships.
Methods:Petkeepingduringpregnancywasascertainedfromwomenresiding
Conclusion: Agene-environmentinteractionbetweenendotoxinandCD14
inadefinedareaofWayneCountyMichiganU.S.A.andrecruitedfromfive
C-260TgenotypeonIgElevelsmaybetheresultofanupstream,opposing
staffmodelobstetricclinics.Maternalvenousbloodwasanalyzedfortotaland
effect on CD4+Foxp3+ and CD4+Foxp3- lymphocyte numbers. Race-
allergen-specificIgEalongwithcordbloodtotalIgEfrom808infants.
ethnicity may influence which of these cell populations is affected by this
Results: During pregnancy, 515 households had no indoor pets and 293
gene-environmentinteraction.
haddogsorcatsinthehome.Ofthese293households,147haddogsonly,96
had cats only, and 50 homes kept both dogs and cats in the home during
pregnancy.Comparedtoinfantsfromhouseholdswithnocatsordogskept
indoorsduringpregnancy,infantswhosehomeshadeithercatsordogshad
significantlyreducedmeancordIgElevels[0.33IU/ml(95%CI0.29Y0.37) 15
versus0.23IU/ml(95%CI0.19Y0.27)p=0.03].Thisassociationwasmost Exposureto animals,allergies andparental education
prominentamongchildrenofmothersthatdidnotexhibitIgEsensitization ChristianApfelbacher1,MarkusOllert2,JohannesRing2,HeidrunBehrendt3,
to common allergens [0.24 IU/ml (95%CI 0.20Y0.30) versus 0.14 IU/ml andUrsulaKraemer4.1BrightonandSussexMedicalSchool,DivisionofPublic
(95%CI0.10Y0.16)p=0.02]andthosewhodidnotsmokeduringpregnancy HealthandPrimaryCare,Brighton,UnitedKingdom;2TechnicalUniversity,
[0.33 IU/ml (95%CI 0.28Y0.37) versus 0.22 IU/ml (95%CI 0.18Y0.27) Department of Dermatology and Allergy Biederstein, Munich, Germany;
p = 0.01]. There was no effect on results when excluding mothers who 3GSF/TechnicalUniversity,DivisionofEnvironmentalDermatology&Allergy,
reportedavoidingpetsduetoallergy-relatedconcerns. Munich,Germany;4Heinrich-Heine-Universitaet,Institutfuerumweltmedizi-
Conclusion:Motherswitheithercatsordogsintheirhomeduringpregnancy, nischeForschung,Duesseldorf,Germany.
especiallythosemotherswhoarenon-sensitizedorarenon-smokers,deliver Background:Studieshaveyieldeddifferentresultsregardingtheassociations
childrenwithlowercordbloodIgElevelscomparedtomotherswhodonotlive between animal exposure and atopy. Whether or not these associations are
with these pets, supporting the hypothesis that pet exposure influences homogeneousacrosssocialstratahasnotyetbeeninvestigated.Toestimatethe
immunedevelopmentinamannerthatisprotectiveforatopyandisoperant associationbetweencurrentanimalexposure(catanddog)andallergicsensi-
evenbeforebirth. tizationandmanifestationsofatopicdiseasesin5to7yearoldschoolbe-
ginners,stratifiedbyparentaleducationallevel.
Methods:30794sixyearoldchildrenparticipatedincross-sectionalstudies
between 1991 and 2000 in Germany. Allergic sensitizations to common
areoallergensasmeasuredbyskinprickandRadioAllergoSorbentTestand
14 symptoms and diagnoses of atopic diseases (asthma, atopic dermatitis, hay
Gene-environment interactionsbetween CD14C-260T fever) were the dependent variables. Exposure to dog and cat were the
andendotoxin exposureonFoxp3+and independentvariables.Logisticregressionwasusedtoadjustforconfounding.
S4 *2007World Allergy Organization
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World AllergyOrganization Journal & November 2007 Abstracts
Analyses were stratified for parental educational level (stratum I, II, III Neck Surgery, Beijing, China; 2Department of Otorhinolaryngology Head
correspondingtoG10years,10yearsand910yearsofschooling). and Neck Surgery, China-Japan Union Hospital, Jilin University, Chang-
Results:Prevalencesofhayfever,eczema,specificsensitizationtopollenand chun, China; 3Hospital of Otolaryngology, First Affiliated Hospital of Sun
housedustmiteandcontacttocatordogweresignificantlydifferentbetween Yat-Sen Universit, Guangzhou, China; 4Department of Otolaryngology,
educational strata. Globally significant associations between cat contact UnionHospital,TongjimedicalCollege,HuazhongU,Wuhan,China;5Ghent
and sensitization to cat (RASTOR 1.92, 95% CI 1.18Y3.11) and hay fever University,DepartmentofOtolaryngology,Ghent,Belgium.
(OR0.61,95%CI0.45Y0.82)remainedsignificantafterstratificationonlyinthe Background: Allergicrhinitis(AR)isacommondiseasewithanincreasing
highesteducationalstratum(OR3.68,95%CI1.90Y7.12andOR0.55,95%CI prevalence.However,littleisknownaboutthecurrentnationalprevalenceofAR
0.36Y0.85).Globallysignificantassociationsofcontacttodogwithsensitization inChina,especiallytheMainlandChina.Theaimofthisstudyistoinvestigate
to pollen (OR 0.71, 95% CI 0.56Y0.89), wheezing (OR 1.31, 95% CI theprevalenceofself-reportedallergicrhinitis;itsassociationwithfactorsof
1.11Y1.55),noseproblems(OR0.72,95%CI0.56Y0.93)andeczema(OR0.84, populations,location,socioeconomicstatus,meteorologyandairpollution;the
95% CI 0.77Y0.92) remained significant in educational stratum II. Globally proportionofpersistentandintermittentallergicrhinitis,aswellasthepercentage
significantassociationsofdogcontactwithsneezingattacks(OR=0.84,95%CI ofundiagnosedsubjectsfrom11maincitiesofthemainlandofChina.
0.71Y1.00)andeczema(OR=0.82,95%CI0.75Y0.91)remainedsignificantin Methods:Telephoneinterviewswereconductedin11maincitiesofthemain-
educationalstratumIII,andinstratumIandIIrespectively. landofChinaaftersamplingtargetphonenumbersbytheapproachofrandom
Conclusion: In 5 to 7 year old German children, differences across social digitaldialing(RDD)viacomputers.AndthequestionnairesinChineseforthe
strataconcerningallergicsensitizations,hayfeverandeczemamaypossiblybe telephoneinterviewsweremostlybasedonthewell-validatedones.
explained by animal exposure differences. Associations between animal Results: A total of 38,203 telephone interviews were conducted from
contactandallergicsensitizationandmanifestationsofatopicdiseasesarenot September2004toMay2005.Theresponserateis63.7%.Theself-reported
homogeneousacrosssocialstrata. prevalenceofallergicrhinitiswasthelowestinXiAn(8.0%),andthehighestis
inUrumqi(21.4%).Thegender-adjustedprevalencerangedfrom8.5%inXiAn
to21.3%inUrumqi;whiletheage-adjustedprevalenceofself-reportedallergic
rhinitisrangedfrom8.7%inBeijingto24.1%inUrumqi.Theadjustedself-
16
reported prevalence of allergic rhinitis was positively correlated with the
Maternalchildhoodexposures,previouspregnanciesandbreast
concentrationofSO2.Withinthesubjectsself-reportingallergicrhinitis,about
milk characteristics:an influenceon offspring`s disease risk?
one-fourth(25.6%)werediagnosedaspersistentallergicrhinitis,andtheother
Petra Amoudruz1, Ulrika Holmlund1, Jens Schollin2, Eva Sverremark- three-fourth (74.4%) were intermittent allergic rhinitis. In addition, the
Ekstro¨m1, and Scott M Montgomery2. 1Wenner-Gren Institute, Stockholm proportion of persistent allergic rhinitis was higher in northern cities than
University, Department of Immunology, Stockholm, Sweden; 2Clinical thatinsoutherncities.Lessthanhalfofthesubjectswithself-reportedallergic
Research Centre O¨rebro University Hospital, Department of Paediatrics, rhinitishadahistoryofvisitingahealthclinic.Amongthem,only37.3%were
O¨rebro,Sweden. previously diagnosed as allergic rhinitis by physicians and 33.1% subjects
Background:Populationsinhighinfectiousexposurecountriesareatlowrisk receivedsurgicaland/ormedicaltreatment.
ofsomeimmune-mediateddiseasessuchasCrohn`sdiseaseandallergy.This Conclusion: Thestudydemonstratesthattheself-reportedprevalenceofal-
low risk ismaintainedonimmigration toan industrialized country, butthe lergicrhinitisin11citiesthroughoutthemainlandofChinahaswidevariations.
offspringofsuchimmigrantshaveahigherimmune-mediateddiseaseriskthan Frequentlysubjectswithself-reportedallergicrhinitiscouldnotbenefitfrom
theindigenouspopulation.Wehypothesizethatearlylifeexposuresinadevel- properdiagnosisortreatment.Subjectswithself-reportedallergicrhinitiswere
oping country shape the maternal immune system, and that this stimulates mostlydiagnosedasintermittentallergicrhinitis,andtheproportionofper-
developmentofheroffspringinamannerinappropriateforthelowinfectious sistentallergicrhinitiswashigherinnortherncitiesthanthatinsoutherncities.
load of a developed county. Other maternal exposures may also influence
diseaseriskinoffspring.
Objective:Toinvestigateifexposuresinchildhood(indicatedbycountryof
18
origin) and subsequent exposures influence immunological characteristics
DetectionofspecificIgEbyproteomicmicroarraysystembased
relevanttostimulationofoffspring.
onallergenicmolecules: a powerfultool forworldwide
Methods: ELISA and Cytometric Bead Array examination of breast milk
epidemiologyof allergic sensitization
componentsamong64mothersresidentinSweden,32ofwhomimmigrated
fromadevelopingcountry. EnricoScala, DonatoQuaratino, Alessandra Zaffiro, Maria Livia Bernardi,
Results:Immigrantsfromadevelopingcountryhadstatisticallysignificantly Rosetta Ferrara, Danila Zennaro, Paola Palazzo, Stefano Ridolfi, Debora
higher levels of breast milk IL-6, IL-8 and TGF-"1. A larger number of Pomponi,MauroGiani,andAdrianoMari.IDI-IRCCS,CenterforClinical
previous pregnancies was associated with down-regulation of several andExperimentalAllergology,Rome,Italy.
substances,statisticallysignificantforsolubleCD14andIL-8. Background: The availability of highly purified natural and recombinant
Conclusion: Childhood exposures influence adult immune characteristics allergenicmoleculesandnanotechnologytoolsappliedtoIgEdetectionallows
potentiallyrelevanttodiseaseriskinoffspring.Suchamechanismmayexplain thecollectionofhugeamountofdatainasingletestforeverysinglesubject.
thehigherimmune-mediateddiseaseriskamongchildrenofmigrantsfroma Thepurposeofthisstudywastoanalysetheprevalenceofallergenicmolecule
developing to developed country.Older siblings may influencedisease risk IgE reactivity within an Italian allergic population and to see whether
throughtheactionofpreviouspregnanciesonmaternalimmunecharacteristics. sensitizationtorareallergenaredetectedaswellasmostcommonones.
ClinicalImplication:Maternalimmunecharacteristicsresultingfromchild- Methods: Sera from consecutive patients claiming for allergic symptoms
hoodexposuresandpreviouspregnanciesmayberelevanttodiseaseriskin causedbyexposureoncontact,inhalation,oringestionwerestudied.Demo-
offspring. graphicandclinicalinformationwererecordedforeachofthem.Aprotein
microarray having 90 spotted natural or recombinant allergenic molecules
(ISAC CRD 90, VBC-Genomics, Austria) has been used for IgE detection
underroutinetestingconditions.Resultswerecollected,storedandanalyzedby
17 customizeddatabasesandprocedures.
Prevalence of self-reported allergic rhinitis inChina Results:12,058consecutiveindividuals(39.2/60.8%male/female,meanage
LuoZhang1,DeminHan1,ZhenDong2,GengXu3,WeijiaKong4,andClaus 32.2T19.1years,range1Y93)havinghistoryofurticaria,rhinitis,asthma,or
Bachert5. 1Beijing Institute of Otolaryngology, Otolaryngology Head and exzemawererecruitedfromMarch2006toJune2007.Patientswithatleast
*2007WorldAllergyOrganization S5
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Abstracts World AllergyOrganization Journal & November 2007
one positive molecule (76% subjects, 42.5/57.5% m/f, and mean age diarrhea are, protein-losing gastroenteropathies. Intestinal lymphangiectasia
31T30.3 yrs) represented our study group. The allergens most frequently (InL).Isarareentitywhichcanbecongenitaloracquireditischaracterized
recognized were from the cypress pollen, Cup a 1 (37.3%), timothy grass byabnormal,dilatedlymphaticsthroughouttheintestinaltract.Thedisorder
pollen,Phlp1(36%),andhousedustmite,Derf2(35%)orDerp2(29%). leads to leakage of lymph causing hypoproteinemia, lymphopenia and
AllergenspecificIgEtoothermoleculesweredetectedlessfrequently(Bosd hypogamaglobulinemia,whichcanleadstodepressionofboththehumoral
726%;Derf123.2%;Parj222.8%;Phlp222.5%;Derp122%;Phlp522%, andcellularimmunesystems.
Parj120%;Olee120%;Feld119.3%;Phlp615.4%).AllergensasBlag2 Case Report: A 35 year old woman from rural Mexico with a history of
andBlag5wererarelypositivedefiningalowexposurebythestudiedcohort. asthma for 20 years, presented with a chief complaint of diarrhea for
Conclusion: Allergenic molecules IgE reactivity detected by microarray 15 months with up to 10 evacuations a day, she referred colic pain with
system represents a powerful, low-invasive and innovative tool for the abdominal distension and flatulence with recurrent symmetrical systemic
molecule-based epidemiology and diagnosis of allergic sensitization. This edema.Thepatientshowedfatigue,weaknessesandmusclespasmsaswellas
applicationallowsgeneratingawealthofinformationotherwisenotavailable myalgiasandfasciculations,shelost22lbsanddevelopedonychomycosisinall
withcurrentsingleplexdiagnostictests. ofhertoenails.Sherecallsshowingthesameclinicalsignsandsymptomsonce
duringchildhood.Hermedicalteamdidnothaveacleardiagnosis.Laboratory
revealedalymphopenia,hypoalbuminemia,hypogammaglobulinemia,hypo-
AUTOIMMUNITY calcemia and negative HIV by ELISA. The stool U¨1-antitrypsin level was
elevated.TheCTofchestandabdomenwasnormal.Anesophagogastroduo-
denoscopy and colonoscopy were performed showing gastritis, a duodenal
19 biopsydemonstratesdilatedlymphaticsandwhitevillispots.
Immunohistochemical staining fordifferential diagnosis of Discussion:Thelackofelevatedlevelsofproteinintheurinealongwiththe
cutaneousgraftversushostdisease and drugreactions depressedserumlevelsofIgGdrewattentiontothegastrointestinaltractasthe
Carolin Weiss1, Walter Burgdorf1, Michael Flaig1, Johanna Tischer2, Julia likelyportalofproteinloss.Detectinganelevatedlevelof"1-antitrypsinina
Tietze1,Hans-JochemKolb2,andAndreasWollenberg1.1Ludwig-Maximilian 24-hour stool collection adds support to the diagnosis of InL. A duodenal
University,Dept.ofDermatologyandAllergy,Munich,Germany;2Ludwig- biopsy with the characteristic histological findings, demonstrating dilated
lymphaticsandwhitespots,confirmedthediagnosis.TreatmentofprimaryInL
MaximilianUniversity,Dept.ofInternalMedicine,Munich,Germany.
issymptomaticandonlymarginallyeffective.Wetreatourpatientwithstrict
Purpose of the Study: Cutanous Graft-versus-Host-Disease (GvHD) may
dietarylipidrestrictions,pancreaticenzymes,probiotics,diuretics,Medium-
show maculopapular rash, bullous dematitis and epidermal necrolysis.
chaintriglyceridesandmultivitamins.Thepatientshowedamarkedresponse
DifferentialdiagnosisofGvHDfromdrugreactionsisdifficultbothclinically
regainedhernormalweight,butthediarrheaandedemasporadicallypresents.
and histologically. The immunobiology of GvHD suggests a key role of
To date is the seventh reported case of primary InL in Mexico and to our
Dendriticcells(DC)inGvHDpathogenesis.Thepresenceofthreedifferent
knowledgetheonlydescribedinliteratureofbiphasicpresentation.
dendriticcellsubsets,i.e.plasmacytoiddendriticcells(PDC),inflammatory
dendritic epidermal cells (IDEC) and Langerhans cells (LC) and other cell
types was analyzed by immunohistochemical staining to improve our
understandingofGvHDimmunobiologyandtoevaluateimmunohistochem-
21
istryasatoolfordifferentialdiagnosisofGvHDanddrugreactions.
Atrial natriuretic peptide receptor(NPRA) signaling inhuman
Methods:SkinbiopsiesofpatientswithclinicallydiagnosedGvHD(n=27)
dendritic cellscontrolstregdevelopment
and drug reactions (n=14) were processed for immunohistochemistry in
Weidong Zhang1, Xueqin Cao1, Gary Hellermann1, Xiaoyuan Kong1,
APAAP technique. Skin sections were stained and semi-quantitatively
Dongqing Chen1, Jia-Wang Wang1, Richard F. Lockey2, and Shyam S.
analyzed for CD1a, CD1b,CD2, CD4, CD8, CD11c, CD20, CD25, CD68,
Mohapatra1.1University of South Florida, Internal Medicine,Tampa, United
CD206,CD207,CD208andCD209,BDCA-2andCCR-7.
ResultsandDiscussion:Arelevantdermalinfiltration(920cellspermm2)of States;2JamesA.HaleyVAHospital,InternalMedicine,Tampa,UnitedStates.
: Thenatriureticpeptides(NP)arekeyendogenousfactorsthatcontrol
BDCA-2+PDCwasspecificforGvHD.ThepresenceofthePDCcorrelated
inflammationandimmunetolerance,thelatterisessentialtomaintainimmune
significantlywiththepresenceofDCexpressingCD1b,CD11candCCR-7.
homeostasis,control autoreactive T cells, prevent the onsetof autoimmune
Hence,thepresenceofmanyPDCsupportstheclinicaldiagnosisofGvHD.
diseasesandachievetoleranceoftransplants.Themechanismofregulationof
CD1aandCD207expressingdermaldendriticcellswerepresentinGvHDand
ANP-NPRAsignalinginDCsiscrucialfortheunderstandingofhowANP
drug reactions, whereas high amounts of CD207 expressing epidermal LC
regulatesinnateimmunityandhowfailureofthissignalingmightcontributeto
were morefrequentlyobservedin GvHD. T cells expressingCD2, CD4 or
autoimmunedisease,chronicinflammationandtissuedamage.Herein,therole
CD8wereequallyobservedinbothpatientgroups.
of the c-terminal NP, ANP and one tolerance inducing NP, NP73-102, in
Conclusion: The observed differences between a PDC dominated dermal
modulating DC function was examined. The results demonstrate that in
infiltrate in GvHD and a myeloid DC dominated dermal infiltrate in drug
contrasttoANP,NP73-102primesDCstoinduceregulatoryT(Treg)cells.The
reactionsshouldbeconfirmedbyanindependentstudy,asthesedifferencesmay
ANP receptor, NPRA, binds to TLR-2, SOCS3 and STAT3 and affects
becomeclinicallyusefulfordifferentialdiagnosisofGvHDfromdrugreactions.
inductionofIL-6,IL-10andTGF-!,notIL-17.SOCS3expressioniscontrolled
inaMyD88-dependentmanner.Also,down-regulationofSOCS3andTLR2,
but not STAT3, affects NPRA expression. These results demonstrate that
TLR2,andSOCS3arekeyplayersinintegratingANP-NPRAsignalingwith
20
innateimmunityandprovideinsightintohowinhibitionofIRNPaffectsANP-
Unusual biphasic presentation of intestinal lymphangiectasia:a
NPRAsignalingpromotingthetolerogenicphenotypeofDCs.
casereport
AlejandroD´ıaz1,SandraN.Gonza´lez-D´ıaz1,GabrielaGalindo1,andDavidA.
Khan2.1UniversityHospitalofMonterrey,AllergyandClinicalImmunology,
Monterrey, Mexico; 2Southwestern Medical Center, Internal Medicine- 22
AllergyandImmunology,Dallas,UnitedStates. Immuneresponse to Rotavirus in thepathogenesis of celiac
Introduction:Chronicdiarrheainadultsisafrequentcauseofconsultation,in disease:moleculareffectsofanti-VP7viralproteinantibodieson
theUnitedStates,withprevalencebetween3Y5%.Amongtherarestcausesof intestinal epithelial cells usinga gene arrayapproach
S6 *2007World Allergy Organization
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World AllergyOrganization Journal & November 2007 Abstracts
G.Zanoni1,M.Dolcino2,A.Peretti1,O.Gabrielli1,G.Tridente1,A.Puccetti2, Keywords:AutoimmuneBullousDiseases,retrospectivestudy.
GiorgioWalterCanonica3,andC.Lunardi4.1UniversityHospital,Department
of Pathology, Immunology Unit, Verona, Italy; 2University of Genoa and
Immunology Unit, Institute G. Gaslini, Histology, Dept of Experimental
Medicine,Genoa,Italy;3GenoaUniversity,DeptofInternalMedicine-DIMI, 24
Genoa,Italy;4UniversityofVerona,InternalMedicine,DeptofClinicaland Autoimmunityin families of IgAD individuals
ExperimentalMedicine,Verona,Italy. Gu8mundur H. Jo¨rgensen1, and Bjo¨rn R. Ludviksson2. 1University of
Background:Celiacdisease(CD)issustainedbyaninappropriateresponse Iceland, Department of Family Medicine, Reykjav´ık, Iceland; 2Landspitali-
againstgluteningeneticallysusceptibleindividuals.Inaddictiontogenetic
UniversityHospital,DepartmentofImmunlogy,Reykjav´ık,Iceland.
and dietary factors, also rotavirus infections have been implicated in CD
Background: The prevalence of autoimmune diseases is thought to be
pathogenesis.SpecificrecognitionofapeptidesharingomologywiththeVP-7
increased among IgA deficient individuals (IgAD). The prevalence of
rotavirusproteinbyseraofCDpatientswithactivediseasehasbeenrecently
autoimmunediseasesamongIgADIcelandicindividualsandtheirfirstdegree
demonstrated.Thisstudyevaluatedthefunctionalmodificationsinducedby
relativeswasinvestigated.Thisisapartofalargerongoingstudyaimedto
anti-viralpeptideantibodiesinintestinalepithelialcells.
evaluate the prevalence, geneaology, complications and thegenetic compo-
Methods:Specificantibodiesdirectedagainsttheviral-derivedVP7peptide
nentsofIgAdeficiency(IgAD)inIceland.
wereaffinity-purifiedfromtheseraofpatientswithactiveCD.Theeffectof
Materials and Methods: Atotal of43IgADindividualshavebeenfound
theseantibodiescross-reactingwithselfantigensonT84intestinalcellswere
through the screening of blood donors (5), re-evaluating IgAD individuals
analyzedwiththegenearraytechnique.Genesup-anddown-regulatedwere
fromapreviousIgADstudyfrom1977(10)andbyevaluatingindividualsthat
identifiedbya2-foldormorechangeinexpression.Theanalysiswasvalidated
were found to have low IgA from 1990 until present at the Institute of
byquantitativePCR.Thedifferentgeneexpressionpatternswereanalyzedby
Laboratorymedicine,Landspitali-UniversityhospitalofIceland(28)Clinical
usingtheArrayAssistisoftware(Stratagene,LaJolla,California,United
evaluation was done by standard questionnaires that focused on symptoms
States)andafunctionalclusterizationwasperformed.
andsignssuggestiveofinfections,allergies,autoimmunityandcancer.
Results: Exposure of T84 cells to anti-VP7 antibodies resulted in the
Results:Amongthe43IgADindividuals,21%werefoundtohavedefinite
upregulationof697transcriptswitha2-foldormoreincreaseinexpression.
autoimmunity(9/43).Ofthose,fourhadtwoormoreautoimmunediseases.
Severalgeneclusterswereupregulatedincludinggenesencodingforchemo-
This is much higher than has been reported for the general population.
kines and molecules involved in inflammation and immune response pro-
Amongstorganspecificautoimmunity,thyroiddieaseswerethemostcommon
cesses,aswellasinapoptosisandcellproliferationregulation.
found(4/9).Whereas,Rheumatoidarthritiswasthemostcommonsystemic
Conclusion:Theexposureofintestinalepithelialcellstoanti-VP7rotavirus
autoimmunityfound(2/9).InfirstdegreerelativeswithIgAD20/43or46.5%
antibodiesmodulatesclustersofgenessimilartothosemodulatedduringCD.
hadhistoryofautoimmunediseases,RA,DMtype1andautoimmunethyroid
Theseresultsconfirmtheimportantroleplayedbyrotavirusinfectioninthe
diseasesbeingthemostcommon.
pathogenesisofceliacdisease.
Conclusion: Autoimmune diseases are common in patents with selective
IgAdeficiency.Sincetheprevalenceofvariousautoimmunityarefoundtobe
highamongstIgADfirstdegreerelatives,thissuggestthatastrongcommon
genetic component could be associated with both conditions. Thus,
23 demonstrating that autoimmunity is an important complications associated
Aretrospectivestudyof autoimmune bullous diseases withIgAdeficiency.
Irma Suryani Idris, Muh Dali Amiruddin, Andi Sastri Zainuddin, and
Khairuddin Djawad. Medical Faculty Hasanuddin University / Dr. Wahidin
MECHANISMS OF ASTHMA I
SudirohusodoGeneralHospital,Dermato-Venereology,Makassar,Indonesia.
Background: Autoimmune Bullous Diseases cause impaired adhesion of
epidermistoepidermalbasementmembraneorimpairedadhesionofepidermal
cellstoeachotherwithcharacterizedbysubstantialmorbidity(pruritus,pain, 26
disfigurement)andinsomeinstance,mortality(secondarytolossofepidermal Acriticalroleforatrialnatriureticpeptidereceptorsignalingin
barrierfunction). allergic disease
Objective:Theaimofthisstudyistoevaluatethefrequencydistributionof Shyam S. Mohapatra1, Xiaoyuan Kong1, Xiaoqin Wang1, Weidong Xu1,
Autoimmune Bullous Diseases (Pemphigus Vulgaris, Pemphigus Foliaceus, Jia-Wang Wang1, Gary Hellermann1, Raji Singham1, Shawna Shirley1,
Bullous Pemphigoid, Cicatrical Pemphigoid, Dermatitis Herpetiformis, PrasannaJena1,WeidongZhang1,SubhraMohapatra2,RichardF.Lockey1,
EpidermolysisBullosa,LinearIgABullousDermatosis). andWilliamGower3.1UniversityofSouthFlorida,InternalMedicine,Tampa,
Methods: A retrospective study was conducted on the medical record of UnitedStates;2H.LeeMoffittCancerCenter,Oncology,Tampa,UnitedStates;
Autoimmune Bullous Diseases patients that visited to Dr. Wahidin 3JamesAHaleyVAHospital,InternalMedicine,Tampa,UnitedStates.
Sudirohusodo General Hospital Makassar, Indonesia for a year (January : Atrial natriuretic peptide(ANP), which has been extensively studied
2006toDecember2006). forcardiovasculareffects,hasreceivedlittleattentionforitsroleinimmunity
Results: In this retrospective study, there were 6 patients of Pemphigus and in inflammation. In humans, ANP modifies airway hyperreactivity,
Vulgaris4malesand 2femaleswithagesbetween19Y35yearsold.Three however,thepreciseroleofANPinthelungsandonlocalinflammationand
patientsofBullousPemphigoid1maleand2females,withagesbetween23Y64 immunityremainstobeestablished.Herein,weshowthatmicedeficientin
yearsold.One male patient of Dermatitis Herpetiformis with age 42 years the atrial natriuretic peptide (ANP) receptor, NPRA, are resistant to
old. Therewas not patient of Pemphigus Foliaceus, Cicatrical Pemphigoid, developing allergen induced pulmonary inflammation, T helper type (Th2)
Linear IgA Bullous Dermatosis, Epidermolysis Bullosa. All patients response and eosinophilia. Chitosan nanocomplexes of a novel peptide,
recoveredfromdisease. NP73-102oraplasmidencodingthepeptide,thatinhibitsNPRAexpression,
Conclusion:Therehasbeenreportedonly10patientsofAutoimmunebullous or a short interference RNA (siRNA) for the NPRA induces bronchopro-
diseases for a year (January 2006 to December 2006) in Dr. Wahidin tective and anti-inflammatory activity including decreased eosinophilia and
SudirohusodoGeneralHospitalMakassar,Indonesia.Thisisararecase.All Th2 cytokines in the lung and reverses asthma in mice. In addition, mice
thepatientsweretreatedbysystemiccorticosteroidandanothertherapiesthat deficientinNPRAandmicewithdecreasedexpressionofNPRAexhibitan
suitableforstandardtherapiesandgivegoodresult. increaseinFoxP3+Tregulatorycells.Together,theseresultsshowthatNPRA
*2007WorldAllergyOrganization S7
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Abstracts World AllergyOrganization Journal & November 2007
signalling may provide a novel target for developing new treatment for assay (EMSA) was performed to check the functional significance of the
asthma. CY1261TpromoterSNP.
Results: The GY1279A promoter polymorphism and the G29968A SNP
showed significant association with atopic asthma (pG0.05). Moreover, the
GY1279AandCY1261Tpromoterpolymorphismwasfoundtobeassociated
27 withserumtotalIgEinthepatients(pG0.05).Atthehaplotypelevel,ATGG
Up-regulationof epithelial andfibroblastprostaglandinD2 was found to be a major risk (pG0.05), while GTGA was found to be a
CRTH2-receptors inasthma protectivehaplotype(pG0.05).Usingelectrophoreticmobilityshiftassay,we
Lena Uller1, Anna Ribbene2, David Sammut2, Peter Howarth2, Stephen demonstrated that the C to T substitution at Y1261 position abolished
Holgate2,andDonnaDavies2.1SouthamptonGeneralHospital,Allergyand transcriptionfactorOct-1bindingsite.
Inflammation Research, Southampton, United Kingdom; 2Southampton Conclusion: TheresultssuggestthatgeneticvariationintheAMCasegene
GeneralHospital,AllergyandInflammationResearch,Southampton,United promoterinfluencessusceptibilitytoasthmaandserumtotalIgE.
Kingdom.
Background:Mastcell-derivedprostaglandinD2(PGD2),nowknowntoact
throughDP1andCRTH2receptorsisregardedacentralmediatorinmany 29
allergicdiseasesincludingasthma.BlockadeofCRTH2receptorshasbeen Directactivation of natural killerT cellsinduces airway
showntoinhibitairwayeosinophiliaandmucusproductioninallergicmice hyperreactivity in a non-humanprimate modelof asthma
(Uller et al Respiratory Research 2007:8:16). However, it is not known if Ponpan Matangkasombut1, Muriel Pichavant2, Takahiro Yasumi2, Carrie
airwaystructuralcellsexpressthesereceptorsor producePGD2.Thus,this Hendricks3, Rosemarie H. DeKruyff1, and Dale T. Umetsu2. 1Children’s
studyexploreswhetherepithelialcellsandfibroblastsobtainedfromasthmatic HospitalBoston,HarvardMedicalSchool,HarvardSchoolofPublicHealth,
andhealthyairwaysexpressCRTH2andDP1receptorsinresponsetofactors Immunology, Boston, United States; 2Children’s Hospital Boston, Harvard
involvedincausingasthmaexacerbation. Medical School, Immunology, Boston, United States; 3Charles River
Methods: Using well-validated cell culture techniques, primary bronchial Laboratories,PreclinicalServices,Worcester,UnitedStates.
epithelialcells(PBECs)andprimarylungfibroblastsfromnormalorasthmatic Background:Inmousemodelsofasthma,weandothersdemonstratedthat
subjects were grown from bronchial brushings and biopsies, respectively. thepresenceofnaturalkillerT(NKT)cellsisrequiredforthedevelopmentof
PBECswereseededin12wellplatesandstimulatedwiththebacterialproduct airwayhyperreactivity(AHR),acardinalfeatureofasthma.Thus,AHRfailed
LPS (0.1Y10 ?g) or virus analogue PolyIC (0.01Y10 ?g). Primary lung tooccurintheabsenceofNKTcells.Furthermore,directactivationofNKT
fibroblastswerestimulatedwiththemediatorsIL-13,TGF-betaandinfected cells with glycolipid antigens alone was sufficient to induce AHR, in the
withtheminorrhinovirusRV1?.Cellswereharvestedatdifferenttimepoints completeabsenceofconventionalCD4+Tcellsandadaptiveimmunity.These
after stimulation using Trizol extraction for RNA. Then mRNA levels for findings indicated that NKT cells are both necessary and sufficient for the
PGD2synthaseanditsreceptorswerequantifiedbyRT-qPCR. inductionofAHRinmice.Moreover,NKTcellsareincreasedinnumberin
Results:PBECsstimulatedwithPoly:ICorLPSresultedinadose-dependent thelungsofpatientswithasthmacomparedtothatofhealthycontrolsubjects
up-regulationoftoll-receptorTLR3andTLR4andproinflammatorycytokines or patients with sarcoidosis, strongly suggesting that NKT cells play an
IL-8,IFN-beta,andIFN-lambda.PBECsstimulatedwithPoly:ICexhibitedno importantroleinhumanasthma.
up-regulation of CRTH2 whereas LPS stimulation dose-dependently up- Purpose:ToexaminethefunctionalroleofpulmonaryNKTcellsinprimates,
regulated the CRTH2 receptor. Neither LPS nor Poly:IC stimulation up- weusedaCynomolgusmonkeymodelofasthma,anddeterminedwhetherthe
regulated DP1-receptors in PBECs. In bronchial fibroblasts the allergic directactivationofpulmonaryNKTcellsresultsinthedevelopmentofAHR.
remodellingcytokines(IL-13andTGF-beta),up-regulatedtheexpressionof Methods:Usingacross-overstudydesigninwhicheachmonkeyservedasits
CRTH2and,additionally,inducedPGD2synthaseproduction. own control, and which minimized the number of monkeys used, we
Conclusion: Wedemonstratethatairwaystructuralcellsinasthmasuchas intratracheallychallengedfourmonkeyswithvehiclecontroloralowdoseof
epithelialcellsandfibroblastsharbourCRTH2-receptorswhicharefurtherup- a´-GalactosylCeramide(a´-GalCer),aglycolipidthatspecificallyactivatesNKT
regulatedatexposuretobacterialproductsandallergiccytokines,respectively. cells. The monkeys were anesthetized, intubated and intratracheally
Hence,studiesonrolesofPGD2and,particularly,CRTH2receptorsinremod- challenged either with vehicle (two monkeys) or a´-GalCer (two monkeys).
ellingofasthmaticairwaysandatexacerbationsofthediseasearewarranted. Twenty-four hours later, AHR was evaluated by measuring airway
resistance and dynamic compliance in response to increasing doses of
methacholine. Six weeks later, the monkeys were again intubated and
challengedwiththealternativetreatment(a´-GalCerorvehicle),followedby
28 assessment of AHR.
Associationof acidic mammalian chitinase(AMCase)with Results: Allfourmonkeystoleratedchallengewitha´-GalCer.Furthermore,
atopicasthmaand serumtotal IgE afterairwaychallengewitha´-GalCer,allfourmonkeysdemonstratedincreased
AHR,significantlygreaterthanthatinducedwiththevehiclecontrol.
Rajshekhar Chatterjee, Jyotsna Batra, and Balaram Ghosh. Institute of
Conclusion:DirectactivationofpulmonaryNKTcellswitha´-GalCerinduced
GenomicsandIntegrativeBiology,Molecularimmunogenetics,Delhi,India.
AHRinanon-humanprimatemodel.Therefore,NKTcellsplayanimportant
Background:AMCase,anenzymeknowntodegradechitin,hasbeenshown
functionalroleinthedevelopmentofAHRinbothmiceandinprimates.
tobehighlyexpressedinasthmaticlungs.Ithasalsobeenshowntocontribute
towards asthma pathogenesis by affecting the IL-13 downstream pathway.
Hence,AMCaseisapotentialcandidateforasthmageneticstudies.
Methods:ToinvestigatetheassociationoftheAMCasepolymorphismsand
haplotypes with atopic asthma and total serum IgE levels in Indian 30
population; Polymorphisms were identified by sequencing 60 unrelated Dolichyl phosphatedependent mechanism ofsteroid resistant
subjects.OnthebasisofLDandheterozygosityindex,atotalofsixSNPs asthmadevelopment
wereshort-listedandfurthergenotypedfor270asthmaticsubjectsand292 Ivans Kuznecovs, Inese Joksta, Sergejs Kuznecovs, and Klara Jegina.
non-asthmatic unrelated controls and were analyzed for genotype and Preventivemedicineresearchlaboratory,AllergyUnit,Riga,Latvia.
haplotype association. The results were confirmed using an independent Background: In most cases of steroid resistant asthma (SRA) there is a
paediatriccohort(Patients=150;Controls=101).Electrophoreticmobilityshift functionalhyporesponsivenessofglucocorticoidreceptors(GR)onTcellsand
S8 *2007World Allergy Organization
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World AllergyOrganization Journal & November 2007 Abstracts
disbalanceinactivityofIL-2,IL-4,IL-10.Dolichylphosphate(DolP)playsan werepositivetoAscarisspp;153(55.84%)toD.pteronyssinus;165(60.22%)
essentialroleincytokinesynthesisandinconstancyofglycoproteinsofthe to B. tropicalis and 84 (30.66%) to B. germanica. In group 1, 146 of the
GR and activity of P-glycoprotein. The present study was carried out to 147Ascarisspp.positivepatients(99.32%)werepositivetoatleast1miteand
estimate the possible role of DolP in mechanism of steroid resistant 142tobothspecies;186patientsinthisgroupwerenegativetoAscarisspp.;in
development. this group 98 (52.69%) were positive to mites (pG0.05). In group 2: 91
Methods:Thesamplesobtainedfrom128patientswithasthma:60patients (33.21%)werepositivetoAscarisspp.andamongthem,81werepositivetoat
withsteroidsensitiveasthma(SSA)and68patientswithSRAandfrom44 least1mitespecies(89.01%);intheAscarisspp.negativegroup(183),97
donors.1)DolichylphosphatewasdefinedinT-cells.2)Alpha-andbeta-GR (53%)werepositivetoatleastonemitespecies(pG0.05).
isoformsexpressionweremeasuredinpatientswithSRAandSSA.3)T-cells Conclusion: Sensitization to Ascaris spp. seems to be a risk factor for
takenfromSRAwereculturedinvitrowithDolP4)P-glycoproteinMDR1 sensitizationtomiteallergensinthetropics.
expression was assessed by immunohistochemical technique 5) Dolichyl
phosphate N-acetylglucosamine-1-phosphate transferase (GPT) due to
DPAGT1polymorphismwasassessedinT-cells.
Results: 1) BloodDolinpatientswithSRAwasincreaseduptosixtimes 32
makingup689.2+47.9ng/mLandurinaryDolconcentrationwasincreased StudyontheFcERI" genepolymorphisminpollen allergic
up to 590.9%, making up to 48.8 + 9.7 mg/mmol in comparison with population of Calcuttacity
SSApatients. 2) The synthesis of DolP was 8.8-10.5-fold decreased in Amitava Roy1, Pampa Chakraborty2, Indrani Roy3, and Swati Gupta
T-lymphocytes in patients with SRA. 3) SRA T-cells membrans contain Bhattacharya4. 1Scottish Church College, Department of Botany, Calcutta,
5,6Y6,4% of P-glycoprotein-170 (the total protein amount) as a resistance India;2SreeChaitanyaCollege-Habra,DepartmentofBotany,Habra,India;
marker.SRAT-cellsdifferfromsensitiveonesinPgpcontentby10-12times.4) 3Institute of Child Health, Allergy Department, Calcutta, India; 4Bose
DolPintheconcentration10Y6Maid7Y9-fold reducing P-glycoprotein-170 Institute,DepartmentofBotany,Calcutta,India.
content in membranes of SRAT-cells to 0,4Y0,6%. 5) T-cells from SRA Background:IgEdependentactivationofmastcellsandbasophilsthrough
patients cultivated with corticosteroids and DolP ( Polyprenols) restore the the high affinity IgE receptor (FcERI$) is involved in the pathogenesis of
possibilitytoinduceIL-10synthesisinvitro.6)TheDolPconcentrationin type 1 respiratory allergy. The FcERI$ gene is located on chromosome
SRAT-cellswasreturnedtothenormallevel.Addingpolyprenoltoculture 11q13,showinglinkagetoatopyandasthma.Mutationsinthisgenecouldalter
ofT-cellsfromSRApatientsenhancedtheexpressionofalphaGPisoforms IL-4 productionand thus modifyIgE levels. Anaminoacid substitutionat
and made these cells more responsive to steroids. position237inthisgenehasbeenreportedtobeassociatedwithatopicasthma
Conclusion: TheresultsshowtheevidencethatDolPisratelimitingmech- phenotypes in Japanese and white population. The present study aims to
anismofsteroidresistanceinasthma,associatedThesituationcanbechanged investigate the relationship between the atopic asthma phenotypes and the
by resistant T-cells treatment with DolP substitute polyprenol. with FcERI$genepolymorphisminthepopulationofCalcuttacity.
hyperactivityofP-glycoproteinandamarkeddefectofGRglycosylationin Method: 232adultpollenallergicpatientsfromCalcuttaparticipatedinan
T-cells.Itis,also,ahypothesis,whichhassuggestedthatthereisagenetic asthma and allergy phenotype- genotype study. Phenotypes obtained by
polymorphismofDPAGT1thatbluntstheresponsetosteroids. studying case history, total and specific IgE, IL-4 level, forced expiratory
volumein1second(FEV1),forcedvitalcapacity(FVC),etc.Genotypingwas
RISK FACTORS FOR ALLERGY done by restriction endonuclease fragment length polymorphism of a
polymerase chain reaction product spanning the E237G polymorphism site
of FcERI$ gene on the DNA samples isolated from the peripheral blood
samplesofstudyandcontrolgroup.
31
Results: Among 232 subjects 44.4% were suffering from allergic rhinitis,
Total IgElevels andinvitro sensitization to Ascaris spp.,
55.6%frombronchialasthmaand19.8%fromcombinationofboth.Theskin
dermatophagoides pteronyssinus, Blomia tropicalisand Blatella
reaction diameter showed positive correlation (pG0.01) with specific IgE,
germanica in thetropical Islandof Martinique
FEV1, IL-4 level and no correlation with total IgE. The restriction
Enrique Ferna´ndez-Caldas. Dr. Beckmann Pharma GmbH, Research & endonuclease fragment length polymorphism study of E237G variant of
Development,Seefeld,Germany. FcERI$geneshowednosignificantdifferencewithcontrolgroup.
Background:Wehavepreviouslydemonstratedthatthepresencedetectable Conclusion: The pollen allergic patients have specific IgE level correlated
specificIgEtoAscarisspp.,increasestheprevalenceofpositiveskinteststo withskinreaction.InthetestedpopulationofCalcuttacityithasbeenfound
commonaeroallergens,especiallymitesandcockroaches,andtofoodaller- thattheE237GvariantofFcERI$geneisnotatallinvolved.
gens,suchasshrimpinMartinique.
Objective:Theobjectiveofthisstudywastoanalysethecorrelationbetween
sensitization to Ascaris spp., total IgE levels, and in vitro sensitization to
Dermatophagoidespteronyssinus,BlomiatropicalisandBlatellagermanica 33
inapopulationofpatientsresidinginthetropicalIslandofMartinique. Dewormingimproves currentwheezeand temporarily
Materials and Methods: 607 consecutive patients (321 females and 286 deterioratesatopy:longitudinalanthelminthictreatmentstudies
males) were evaluated at a local allergy clinic for allergic respiratory in Cubanschoolchildren
complaintsfromFebruary2003toMarch2007.Meanagewas20.36(1Y75 Meike Wo¨rdemann1, Joris Menten2, Raquel Junco Diaz3, Lenina Menocal
years).SpecificIgEwasdeterminedbytheCAPmethod(Phadia).Thepatients Heredia3,AniranRuizEspinosa4,BrunoGryseels5,MarianoBonetGorbea6,
weredividedinto2groups:Group1:333patientswithG15yearsofage,and andKatjaPolman1.1InstituteofTropicalMedicine,ParasitologyDepartment,
Group2:274patientswith915yearsofage. Antwerp, Belgium; 2Institute of Tropical Medicine, Clincial Sciences
Results: Mean total IgE levelsinthe studied population was 752.03kU/L Department,Antwerp,Belgium;3NationalInstituteofHygiene,Epidemiology
(2Y39.888);238patients(39.2%)hadapositivespecificIgEdeterminationto and Microbiology, Research Department, Havana, Cuba; 4Institute Pedro
Ascarisspp;387(63.76%)toD.pteronyssinus;399(65.73%)toB.tropicalis Kouri, Parasitology Department, Havana, Cuba; 5Institute of Tropical
and 218 to B. germanica (35.9%). In Group 1: mean total IgE levels: Medicine, Director, Antwerp, Belgium; 6National Institute of Hygiene,
987.83 kU/L (2.13Y39.888); 147 (44.14%) were positive to Ascaris spp.; EpidemiologyandMicrobiology,Director,Havana,Cuba.
234 (70.27%) to D. pteronyssinus and B. tropicalis and 134 (40.24%) to Background:Although helminth infections have been suggestedto protect
B.germanica.Ingroup2,meantotalIgE:465.46kU/L(2Y8.453);91(33.2%) from atopy and atopic diseases, there is still no consensus on their
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Abstracts World AllergyOrganization Journal & November 2007
relationship. We investigated the effect of deworming and intestinal to 32.7% (95% CI: 24.7Y42.9%) (pG0.001) and subsequently returned to
helminth (re)infections on atopy, asthma, allergic rhinoconjunctivitis and baseline values (11.9%, 95% CI: 6.9Y19.6%). (Re)infection with A.
atopic dermatitis. lumbricoides and T. trichuria was positively and hookworm negatively
Methods: We examined 440 4Y13 year-old Cuban schoolchildren in six- associatedwiththedevelopmentorretentionoftheseatopicdiseases,whilefor
monthlyintervalsfor24months.Intestinalhelminthinfectionswerediagnosed atopyanoppositetrendwasseen.
bystoolexamination.AtopicdiseaseswerediagnosedbyISAAC(International Conclusion:Ourdataindicatethatatopicdiseasesimproveafteranthelminthic
Study of Asthma and Allergies in Childhood) questionnaire, asthma treatment.Atopyontheotherhandincreasesafterdeworming.Asthisincrease
additionallybyspirometry,andatopybyskinpricktesting(SPT). appearsonlytemporarily,dewormingofschoolchildrendoesnotseemtobea
Results: After deworming the frequency of current wheeze (pG0.001) and risk factor for the development of atopy, nor for atopic disease. Effects of
allergic rhinoconjunctivitis (p=0.015) significantly decreased. The percen- helminth (re)infections on atopy and atopic diseases appear to be species-
tageofSPTpositivestemporarilyincreasedfrom9.7%(95%CI:5.5Y16.6%) specific.
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