哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤

哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤Typesofallergies2021/4/272Allergen

Any

substance

often

a

protein

that

induces

an

allergy

Commonallergens過(guò)敏原種類(lèi)很多“除了水、葡萄糖和鹽之外都可以成為過(guò)敏原”2021/4/273Commoncoldorallergy2021/4/274AsthmaDerivedfromtheGreekrootασθμαινωOriginallydidnotdefineadisease,butwasemployedtodescriberespiratorysymptomsofavarietyofpulmonaryconditionsBythebeginningofthe20thcentury,

asthma

wasseentobeauniqueillnesscharacterizedby'spasmodicafflictionsofthebronchialtubes'.Today,

asthma

isseenasachronicinflammatorydiseasewhichisnotyetfullyunderstoodinitspathophysiologyTherapyisstillonthepathtobecomingoptimal.BergmannKC.Asthma.ChemImmunolAllergy.2014;100:69-80.2021/4/275盲人摸象2021/4/2762014GINA哮喘表型Allergicasthma:usuallyrespondwelltoinhaledcorticosteroid(ICS)treatmentNon-allergicasthma:oftenrespondlesswelltoICS.Late-allergicasthma:someadults,particularlywomen,patientwithasthmaforthefirsttimeinadultlife.Thesepatientstendtobenon-allergic,andoftenrequirehigherdosesofICSorarerelativelyrefractorytocorticosteroidtreatmentAsthmawithfixedairflowlimitation:somepatientswithlong-standingasthmadevelopfixedairflowlimitationthatisthoughttobeduetoairwaywallremodeling.Asthmawithobesity:someobesepatientswithasthmahaveprominentrespiratorysymptomsandlittleeosinophilicairwayinflammation.GINAGuidelinesforAsthma20142021/4/277Terminologyofallergicphenomena'idiosyncrasy'-'antipathy'-'Hypersensitivity'-'Anaphylaxis'-'allergyA.F.CocaandR.A.Cookeintroducedtheterm'atopy'：'hypersensitiveness'occurredspontaneously'atopy'gainedanewsense,sinceIgEisacharacteristic-Clinicallysimilardiseasessuchasasthma,rhinoconjunctivitisoreczemacanbefoundintheabsenceofIgE,andarethencalled'intrinsic'variantsofthesamediseaseChemImmunolAllergy.2014;100:46-52.2021/4/278CoombsandGell’sClassificationofHypersensitivity2021/4/279Does"intrinsic"asthmaexist?Tentofortypercentofasthmaticsare"intrinsic"Analysisofbronchialmucosalexpressionof"pro-eosinophilic"and"pro-atopic"markers[IL-3,-4,-5,-13,GM-CSF,RANTES,MCP-3,IgEandhighaffinityIgEreceptor(FcepsilonRI)]ThereweremoresimilaritiesthandifferencesinimmunopathologybetweenatopicandnonatopicHumbertM.Does"intrinsic"asthmaexist?RevMalRespir.2000Feb;17(1Pt2):245-54..2021/4/2710Allergicvsnonallergicasthma:

whatmakesthedifference?Nonallergic：Greaterage,femalesex,sinusalpolyposis,andFEV1below80%ofthepredictedvalueAllergic：historyofhayfever,seasonalexacerbationofasthma,andasthmadurationAllergy.2002Jul;57(7):607-13.2021/4/2711Asthmaphenotypes:nonallergic(intrinsic)asthma.Thedefinition：subjectswithasthmaandwithwhomallergicsensitizationcannotbedemonstratednegativeskinpricktestorinvitrospecific-IgEtesttoapanelofseasonalandperennialallergensNonallergicasthmaoccursin10%to33%ofindividualswithasthmaandhasalateronsetthanallergicasthma,withafemalepredominance.NonallergicasthmaappearstobemoreseverethanallergicasthmainmanycasesandmaybelessresponsivetostandardtherapyPetersSP.Asthmaphenotypes:nonallergic(intrinsic)asthma.JAllergyClinImmunolPract.

2014Nov-Dec;2(6):650-2..2021/4/2712Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.ControversieshaveemergedinrelationtothisconceptNotfindingspecificallergensensitizationinanasthmaticpatientneitherexcludesanallergiccomponentnortheessentialrolethatimmunoglobulinEmayplayinasthmaTheatopicstatusisoneamongmanyotherquestionsOmalizumab,theonlymonoclonalanti-immunoglobulinEantibodycommercializedforasthma,shouldbetriedinpatientswithuncontrolledsevereasthmaindependentoftheiratopicstatus

VenneraMdelC1,

PicadoC1.Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.IntJGenMed.

2014

Jul8;7:365-71.2021/4/2713哪些哮喘患者需要行AIT？過(guò)敏的概念總tIgE2021/4/2714SentietalAllergy2011;66(6):7981911Noon1thSCIT1950s1thSCITControlStudy;1980s1thDBPCSLIT;2000s1thsublingualTablet2011sInnovatingforpatientbenefit100yeasofantigenspecificimmunotherpy2021/4/2715Allergenspecificimmunotherapy2021/4/2716Self-amplificationmechanismsofmastcellactivation:

anewlookinallergy.Thecurrentdefinitionofallergy,agroupofIgEmediateddiseasesappearsdifficulttocoverallallergicreactionsSinceevenIgEdependentallergicreactionsarecarriedoutthroughactivationofmastcellsandbasophils,andallallergensmentionedabovecanactivatethesecellswehypothesizethatallergicreactionsaremastcellandbasophilmediatedinflammatoryprocessasitistheactivatedmastcellsandbasophilsthatinitiatethepathologicalprocessoftheimmediateallergicreactionswhereas

IgEonlyservesasoneoftheactivatorsofthesecells.HeS,ZhangH,ZengX,YangP.CurrMolMed.2012Dec;12(10):1329-39.2021/4/27172021/4/2718過(guò)敏性疾病實(shí)驗(yàn)室診斷的理想程序皮試、斑貼試驗(yàn)↓（陽(yáng)性）過(guò)敏原、半抗原或小分子物質(zhì)↓嗜堿性粒細(xì)胞/肥大細(xì)胞激發(fā)試驗(yàn) ↓（陽(yáng)性）（陰性基本排除急性過(guò)敏）

特異性IgE、IgG檢測(cè)

（陰性）

（陽(yáng)性）

（陽(yáng)性）

類(lèi)過(guò)敏反應(yīng)IgE依賴(lài)性IgG依賴(lài)性

↓

（目前定義為過(guò)敏）（目前定義為食物不耐受）

避免接觸類(lèi)過(guò)敏原

↓↓（IgG陽(yáng)性）

脫敏療法的適應(yīng)癥低敏食物、食物脫敏？2021/4/2719AIT適應(yīng)癥--中國(guó)專(zhuān)家共識(shí)2021/4/2720AIT禁忌癥-中國(guó)專(zhuān)家共識(shí)2021/4/2721哮喘患者AIT現(xiàn)狀2021/4/27222021/4/2723結(jié)論2021/4/27242021/4/2725SublingualimmunotherapyIncluded5,131patientsfrom63studieswereanalyzedthatsublingualimmunotherapyimprovessymptomsofasthmareducestheuseofasthmamedicationsimprovesthequalityoflifeLinetal.Sublingualimmunotherapyforthetreatmentofallergicrhinoconjunctivitisandasthma:asystematicreview.JAMA2013;309:1278-882021/4/27262021/4/27272021/4/2728AIT的安全性2021/4/2729哮喘AIT困惑與思考2021/4/2730過(guò)敏原識(shí)別過(guò)敏原的特異性診斷查找過(guò)敏原是與其他學(xué)科的基本區(qū)別2021/4/2731IgE介導(dǎo)變態(tài)反應(yīng)的診斷AllergicrhinitisanditsimpactonasthmaAllergy,2008,s1-153.2021/4/2732體內(nèi)試驗(yàn)-皮膚試驗(yàn)皮內(nèi)試驗(yàn)I型速發(fā)性變態(tài)反應(yīng)點(diǎn)刺試驗(yàn)I型速發(fā)性變態(tài)反應(yīng)斑貼試驗(yàn)IV型遲發(fā)型變態(tài)反應(yīng)2021/4/2733常用過(guò)敏原點(diǎn)刺液種類(lèi)螨屬：戶(hù)塵螨、粉塵螨、熱螨、倉(cāng)儲(chǔ)螨寵物毛發(fā)皮屑：貓毛、狗毛樹(shù)木花粉：榿木、榛屬、楊屬、榆科、柳屬、懸鈴木雜草花粉：蒿草、豚草、葎草、雞足草、酥油草、毒麥、梯牧草、牧場(chǎng)草作物花粉：向日葵、玉米真菌：鏈格孢、毛殼菌、芽枝霉、鐮刀菌、青霉、擴(kuò)展青霉、點(diǎn)青霉蟑螂：德國(guó)小蠊、美洲大蠊2021/4/2734體外試驗(yàn)-sIgE檢測(cè)嚴(yán)重皮炎不能作皮試者皮試假陽(yáng)性的劃痕癥患者皮膚反應(yīng)差的老年人及3歲以下兒童用藥的影響嚴(yán)重過(guò)敏狀態(tài)發(fā)作者對(duì)作皮試時(shí)產(chǎn)生的不適恐懼者對(duì)過(guò)敏嚴(yán)重度評(píng)估擬行特異性免疫治療者2021/4/2735我國(guó)過(guò)敏原體外診斷種類(lèi)RAST-放射過(guò)敏原吸附試驗(yàn)FEIA-固相熒光酶免疫技術(shù)（CAP）免疫印跡技術(shù)（AS）ELISA-酶聯(lián)免疫吸附試驗(yàn)免疫捕獲法（酶聯(lián)免疫吸附試驗(yàn)中之一種）過(guò)敏原芯片：固相／液相免疫化學(xué)發(fā)光法過(guò)敏原誘發(fā)組胺釋放試驗(yàn)：期望能解決IgE不能解決的問(wèn)題2021/4/2736五種免疫球蛋白的血漿濃度

（mg/dL）IgG1200（40000）IgM150（5000）IgA300（10000）IgD3（100）IgE0.03（1）血中IgE含量甚微，僅為血中IgG的四萬(wàn)分之一特異性IgE含量則更甚微2021/4/2737一般的免疫學(xué)方法測(cè)不到sIgE放射過(guò)敏原吸附試驗(yàn)(RAST)

熒光免疫標(biāo)記分析法ELISA（酶聯(lián)免疫吸附測(cè)定）蛋白芯片檢測(cè)熒光酶免法（ImmunoCAPSweden）是檢測(cè)的金標(biāo)準(zhǔn)2021/4/2738總IgE的意義總IgE沒(méi)有正常值，只定上限端值，兒童50KU/L成人60KU/L新生兒的總IgE很低，隨年齡增長(zhǎng)升高，10-15歲達(dá)頂峰，以后又逐步下降，男性高于女性理想的情況下，總IgE應(yīng)該是0或極低2021/4/2739