臨床免疫學(xué)：臨床免疫學(xué)總論完整版

臨床免疫學(xué)總論

2總論提綱一、免疫相關(guān)基本概念二、臨床免疫相關(guān)疾病三、臨床免疫相關(guān)機(jī)構(gòu)四、臨床免疫相關(guān)技術(shù)五、臨床應(yīng)用相關(guān)進(jìn)展六、國內(nèi)外的應(yīng)用指南3一、免疫相關(guān)基本概念4Immunis--免除瘟疫

ThefirstrecordedattemptstoinduceimmunitydeliberatelywereperformedbytheChineseinthe15thcentury.In1718,LadyMaryWortleyMontagu,thewifeoftheBritishambassadortoConstantinople,observedthepositiveeffectsofvariolationonthenativepopulationandhadthetechniqueperformedonherownchildren.ThemethodwassignificantlyimprovedbytheEnglishphysicianEdwardJenner,in1798.Immunology,5thed,Oct2002,byRichardA.GoldsbyIn1885,Pasteuradministeredhisfirstvaccinetoahuman,ayoungboywhohadbeenbittenrepeatedlybyarabiddog5‘prophylacticimmunization’inancientChinesemedicinebooks

葛洪(283-363)：肘后備急方孫思邈(581-682)：備急千金要方CaoX.NatureImmunology2008;9(4)6GeraldM.EdelmanBorn:1July1929,NewYork,NY,USAAffiliationatthetimeoftheaward:RockefellerUniversity,NewYork,NY,USARodneyR.PorterBorn:8October1917,Newton-le-Willows,UnitedKingdomDied:6September1985,Winchester,UnitedKingdomAffiliationatthetimeoftheaward:UniversityofOxford,Oxford,UnitedKingdom1972NobelPrize:"fortheirdiscoveriesconcerningthechemicalstructureofantibodies"7SusumuTonegawaBorn:6September1939,Nagoya,JapanAffiliationatthetimeoftheaward:MassachusettsInstituteofTechnology(MIT),Cambridge,MA,USA1987NobelPrize:"forhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity"8GeorgesJ.F.K?hlerBorn:17April1946,Munich,GermanyDied:1March1995,FreiburgimBreisgau,GermanyAffiliationatthetimeoftheaward:BaselInstituteforImmunology,Basel,SwitzerlandCésarMilsteinBorn:8October1927,BahiaBlanca,ArgentinaDied:24March2002,Cambridge,UnitedKingdomAffiliationatthetimeoftheaward:MRCLaboratoryofMolecularBiology,Cambridge,UnitedKingdom1984NobelPrize:"fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprincipleforproductionofmonoclonalantibodies"9BarujBenacerrafBorn:29October1920,Caracas,VenezuelaDied:2August2011,Boston,MA,USAAffiliationatthetimeoftheaward:HarvardMedicalSchool,Boston,MA,USAJeanDaussetBorn:19October1916,Toulouse,FranceDied:6June2009,Palma,Majorca,SpainAffiliationatthetimeoftheaward:UniversitédeParis,LaboratoireImmuno-Hématologie,Paris,FranceGeorgeD.SnellBorn:19December1903,Bradford,MA,USADied:6June1996,BarHarbor,ME,USAAffiliationatthetimeoftheaward:JacksonLaboratory,BarHarbor,ME,USA1980NobelPrize:"fortheirdiscoveriesconcerninggeneticallydeterminedstructuresonthecellsurface(MHC)thatregulateimmunologicalreactions"10PeterC.DohertyBorn:15October1940,Brisbane,AustraliaAffiliationatthetimeoftheaward:St.JudeChildren'sResearchHospital,Memphis,TN,USARolfM.ZinkernagelBorn:6January1944,Basel,SwitzerlandAffiliationatthetimeoftheaward:UniversityofZurich,InstituteofExperimentalImmunology,Zurich,Switzerland1996NobelPrize:"fortheirdiscoveriesconcerningthespecificityofthecellmediatedimmunedefence(MHC-Ag-TCR)"11JulesBordetBorn:13June1870,Soignies,BelgiumDied:6April1961,Brussels,BelgiumAffiliationatthetimeoftheaward:BrusselsUniversity,Brussels,Belgium1919NobelPrize:"forhisdiscoveriesrelatingtoimmunity(complement)"*receivedhisNobelPrizeoneyearlater,in1920.

12IlyaIlyichMechnikovBorn:16May1845,Kharkov(nowKharkiv),RussianEmpire(nowUkraine)Died:16July1916,Paris,FranceAffiliationatthetimeoftheaward:InstitutPasteur,Paris,France1908NobelPrize:"inrecognitionoftheirworkonimmunity(phagocytosis)"13BruceA.BeutlerBorn:1957,Chicago,IL,USAAffiliationatthetimeoftheaward:UniversityofTexasSouthwesternMedicalCenteratDallas,Dallas,TX,USA,TheScrippsResearchInstitute,LaJolla,CA,USAJulesA.HoffmannBorn:1941,Echternach,Luxembourg2011NobelPrize:"fortheirdiscoveriesconcerningtheactivationofinnateimmunity"14RalphM.SteinmanBorn:1943,Montreal,CanadaDied:30September2011Affiliationatthetimeoftheaward:RockefellerUniversity,NewYork,NY,USA2011NobelPrize:"forhisdiscoveryofthedendriticcellanditsroleinadaptiveimmunity"15Clinicalandlaboratorydisciplinedealingwiththediagnosisandmanagementofdiseasesinwhichtheimmunesystemisinvolvedineitherpathogenesisortreatmentorboth.

ClinicalImmunologists

ClinicalLaboratoryImmunologistsDefinitionofClinicalImmunologyFaheyJL.TheImmunologist1995;3(3):10416二、臨床免疫相關(guān)疾病17Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.Cancers

7.TransplantationsClinicalImmunology18Fran?oiseBarré-SinoussiBorn:30July1947,Paris,FranceAffiliationatthetimeoftheaward:RegulationofRetroviralInfectionsUnit,VirologyDepartment,InstitutPasteur,Paris,FranceLucMontagnierBorn:18August1932,Chabris,FranceAffiliationatthetimeoftheaward:WorldFoundationforAIDSResearchandPrevention,Paris,France2008NobelPrize:"fortheirdiscoveryofhumanimmunodeficiencyvirus"上海市HIV檢測量20Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.cancers

7.TransplantationsClinicalImmunology21Immunoelectrophoresis(-)(+)22FixedImmunoelectrophoresis23Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.cancers

7.TransplantationsClinicalImmunology24CharlesRobertRichetBorn:26August1850,Paris,FranceDied:4December1935,Paris,FranceAffiliationatthetimeoftheaward:SorbonneUniversity,Paris,France1913NobelPrize:"inrecognitionofhisworkonanaphylaxis"25Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.cancers

7.TransplantationsClinicalImmunology26DCTBYYYY自身免疫與自身免疫性疾病27自身免疫性疾病種類累及各個器官，已知的有80多種神經(jīng)系統(tǒng)疾病內(nèi)分泌系統(tǒng)皮膚和其它結(jié)締組織眼睛、血液和血管系統(tǒng)28自身免疫性疾病流行情況

中國 4100萬巴西 580萬墨西哥330萬德國260萬法國190萬俄羅斯450萬伊朗

210萬埃及240萬埃塞俄比亞 230萬印度 3300萬加拿大 100萬泰國 200萬29Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.cancers

7.TransplantationsClinicalImmunology30BaruchS.BlumbergBorn:28July1925,NewYork,USADied:5April20111976NobelPrize:"forhisdiscoveriesconcerningnewmechanismsfortheoriginanddisseminationofinfectiousdiseases"31Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.Cancers

7.TransplantationsClinicalImmunology32前十位惡性腫瘤死亡率順位2004-20051990-19921973-1975疾病名稱死亡率(1/10萬)疾病名稱死亡率(1/10萬)疾病名稱死亡率(1/10萬)1肺癌30.83胃癌25.16胃癌19.542肝癌26.26肝癌20.37食管癌18.833胃癌24.71肺癌17.54肝癌12.544食管癌15.21食管癌17.38肺癌7.095結(jié)直腸癌7.25結(jié)直腸癌5.30子宮頸癌5.236白血病3.84白血病3.64結(jié)直腸癌4.607腦瘤3.13子宮頸癌1.89白血病2.728女性乳腺癌2.90鼻咽癌1.74鼻咽癌2.329胰腺癌2.62女性乳腺癌1.72女性乳腺癌1.6510骨癌1.70

總計134.80

108.26

83.653334HaraldzurHausenBorn:11March1936,Gelsenkirchen,GermanyAffiliationatthetimeoftheaward:GermanCancerResearchCentre,Heidelberg,Germany2008NobelPrize:"forhisdiscoveryofhumanpapillomavirusescausingcervicalcancer"35Sevencategoriesofdiseases:

1.Immunodeficiencies

2.Immunoproliferativediseases

3.Allergies

4.Autoimmunediseases

5.Infectiousdiseases

6.cancers

7.TransplantationsClinicalImmunology36PeterBrianMedawarBorn:28February1915,RiodeJaneiro,BrazilDied:2October1987,London,UnitedKingdomAffiliationatthetimeoftheaward:UniversityCollege,London,UnitedKingdom1960NobelPrize:"fordiscoveryofacquiredimmunologicaltolerance"37ClinicalLaboratoryImmunologySpecificantibodiesto:

microbialantigens;autoantigens;alloantigens;allergensImmunochemistry

immunoglobulinsandtheirfragments;cytokines;complements;acutephaseproteins;specificplasmaproteins;etcCellularstudies lymphocytemarkers;HLAtyping;functionsImmunohistology lymphnodes;renalandskinbiopsiesMolecularbiology

clonality;specificorrelatedgene38三、臨床免疫相關(guān)機(jī)構(gòu)39IUISCommittees(1971)NomenclatureSubcommittee(1971)EducationCommittee(1971)QualityAssessmentandStandardizationCommittee(1971)ClinicalImmunologyCommittee(1973)VeterinaryImmunologyCommittee(1980)PrimaryImmunodeficiencyExpertCommittee(2008)GenderEqualityandCareerDevelopmentCommittee(2010)ImmunotherapyCommitteeVaccineCommittee40我國臨床免疫學(xué)學(xué)術(shù)機(jī)構(gòu)中國免疫學(xué)會(1985)

臨床免疫學(xué)會(1990)中華醫(yī)學(xué)會風(fēng)濕病學(xué)會等(1985)

…

…

檢驗醫(yī)學(xué)學(xué)會(1980)

臨床免疫委員會41

專業(yè)分會

腫瘤免疫分會

主任委員：曹雪濤

通訊地址：上海市翔殷路800號

上海第二軍醫(yī)大學(xué)免疫學(xué)研究所（200433）

電話/p>

E-mail：caoxt@

基礎(chǔ)免疫分會

主任委員：吳長有

通訊地址：廣州市中山二路74號

中山大學(xué)中山醫(yī)學(xué)院免疫學(xué)教研室（510089）

電話/p>

E-mail：changyou_wu@

神經(jīng)免疫分會

主任委員：許賢豪

通訊地址：北京市東城區(qū)大華路1號

衛(wèi)生部北京醫(yī)院（100730）

電話/p>

E-mail：xuxh@

血液免疫分會

主任委員：王德炳

通訊地址：北京市西直門南大街11號北京大學(xué)人民醫(yī)院（100044）

電話5070

E-mail：wangdb@臨床免疫分會

主任委員：仲人前

通訊地址：上海市鳳陽路415號

上海長征醫(yī)院（200003）

電話73631

E-mail：rqzhong@

中醫(yī)藥免疫分會

主任委員：王培訓(xùn)

通訊地址：廣州市機(jī)場路12號

廣州中醫(yī)藥大學(xué)臨床基礎(chǔ)研究所（510405）

電話/p>

E-mail：wpx@

生殖免疫分會

主任委員：歐汝強(qiáng)

通訊地址：廣東省廣州市梅東路17號

廣東省計劃生育研究所（510600）

電話/p>

E-mail：qianggd@126.com

獸醫(yī)免疫分會

主任委員：孔憲剛

通訊地址：哈爾濱市南崗區(qū)馬端街427號

中國農(nóng)業(yè)科學(xué)院哈爾濱獸醫(yī)研究所（150001）

電話/p>

E-mail：xgkong@

名詞審定委員會

主任委員：葛錫銳

通訊地址：上海市岳陽路320號

中國科學(xué)院細(xì)胞庫（200031）

電話/p>

E-mail：gexirui@

42四、臨床免疫相關(guān)技術(shù)臨床免疫學(xué)技術(shù)經(jīng)典免疫學(xué)技術(shù)現(xiàn)代免疫學(xué)技術(shù)1890Behring白喉抗毒素（1901Nobel）1958EdelmanGM,PorterRR免疫球蛋白結(jié)構(gòu)(1972Nobel)1974TonegawaS免疫球蛋白基因(1987Nobel)臨床免疫學(xué)技術(shù)經(jīng)典免疫學(xué)技術(shù)凝集反應(yīng)

沉淀反應(yīng)

溶血反應(yīng)

免疫電泳1896MaxG,HerbertD細(xì)菌凝集；1902LandersteinerK血型凝集（1930Nobel）1897RudolphK；1948JacqueO,OrjanO免疫擴(kuò)散（1976NobelforHBVBlumbergBS)1894RichardP免疫溶菌；1901JulesB,OctaveG補(bǔ)體結(jié)合試驗1939TiseliusAW,KabatEA蛋白電泳；1955GrabarP,WilliamsC免疫電泳臨床免疫學(xué)技術(shù)現(xiàn)代免疫學(xué)技術(shù)免疫比濁技術(shù)免疫細(xì)胞技術(shù)免疫標(biāo)記技術(shù)1964BainB混合淋巴細(xì)胞培養(yǎng)；1970GaliliU,CoombsRA玫瑰花環(huán)試驗；1975MilsteinC,KohlerG單克隆抗體技術(shù)（1984Nobel)1941CoonsAH免疫熒光；1960YalowR,BersonS放射免疫檢測(1977Nobel)(1922BantinFG胰島素與糖尿病(1923Nobel)；1971EngvallE,PerlamanPELISA；ELISPOT；1971FaulkWP,TaylorGM免疫膠體金；1972流式細(xì)胞術(shù)1978VelanB,HalmanM化學(xué)發(fā)光；1981StarkG免疫印跡；1992TakeshiS免疫PCR；1996AltmanJDMHC四聚體技術(shù)2000s電化學(xué)發(fā)光；2000s抗體/抗原芯片1977SeternberyMJ速率散射比濁OuchterlonydoubleimmunodiffusionABAnti-AAAAnti-AABAnti-ABBABAnti-AB47CounterImmunoelectrophoresis48ManciniradialimmunodiffusionAb49Rocketimmunoelectrophoresis+-Ab50Redbloodcellagglutination51檢測器A(透射濁度法)檢測器B(散射濁度法)

I0I渾濁樣品光源TurbidimetryandNephlometry52Immunofluorescence53OsamuShimomuraBorn:27August1928,Kyoto,JapanAffiliationatthetimeoftheaward:MarineBiologicalLaboratory(MBL),WoodsHole,MA,USA,BostonUniversityMedicalSchool,Massachusetts,MA,USAMartinChalfieBorn:15January1947,Chicago,IL,USAAffiliationatthetimeoftheaward:ColumbiaUniversity,NewYork,NY,USARogerY.TsienBorn:1February1952,NewYork,NY,USAAffiliationatthetimeoftheaward:UniversityofCalifornia,SanDiego,CA,USA,HowardHughesMedicalInstitute2008NobelPrizeforchemistry:"forthediscoveryanddevelopmentofthegreenfluorescentprotein,GFP"54Radioimmunoassay55RosalynYalowBorn:19July1921,NewYork,NY,USADied:30May2011,NewYork,NY,USA1977NobelPrize:"forthedevelopmentofradioimmunoassaysofpeptidehormones"56Enzyme-LinkedImmunoSorbentAssay57Chemiluminescenceimmunoassay58Johnson&JohnsonVitrosECiLuminol(基態(tài)）Luminol(激發(fā)態(tài)）light增強(qiáng)劑(基態(tài)）增強(qiáng)劑(激發(fā)態(tài)）Luminol(基態(tài))Luminol(激發(fā)態(tài))lightHRPHRP未增強(qiáng)化學(xué)發(fā)光增強(qiáng)化學(xué)發(fā)光59AbbottChemiflexTM

、SiemensCentaur專利的穩(wěn)定(sulfopropyl)基團(tuán)專利的發(fā)光(sulfonamide)基團(tuán)60經(jīng)過最后一步?jīng)_洗,磁微粒子上捕捉有免疫復(fù)合物Pre-Trigger被加入Pre-Trigger使專利的吖啶酯標(biāo)記物從固相載體上釋放到溶液中磁塊吸附磁微粒子被磁塊吸附在反應(yīng)杯的壁上,從而防止磁粒子對光信號檢測的干擾Trigger被加入提供一個堿性環(huán)境產(chǎn)生光信號吖啶酯標(biāo)記物被釋放產(chǎn)生光信號產(chǎn)生的信號以RelativeLightUnit(RLU)方式表達(dá).61BeckmanAccess、DPCImmuliteAMPPD:堿性磷酸酶底物3-(2-螺旋金剛烷)-4-甲氧基-4-(3-磷氧酰)-苯基-1,2-二氧環(huán)乙烷

62RocheECL63RocheECL64FlowCytometry65ImmunoassaysandTheirCharacteristics

Labels(ReporterGroups)B/FSeparation[*]SignalDetectionSensitivityPrecipitationimmunoassaysNotrequiredNotrequiredNakedeye,turbidity,nephrometry≈10μg/mL(1)ParticleimmunoassaysBloodcells,artificialparticles(gelatin,particles,latex,etc.)NotrequiredNakedeye,patternanalyzer,spectrophotometry,particlecounting≈5ng/mL(2)RadioimmunoassaysRadioisotopes(125I,3H)RequiredPhotoncounting≈5pg/mLEnzymeimmunoassaysEnzymesRequiredSpectrophotometry,fluorometry,photoncounting≈5pg/mL

≈0.1pg/mL(3)(CL-EIA)FluorescentimmunoassaysFluorophoresRequiredPhotoncounting≈5pg/mL(4)ChemiluminescentimmunoassaysChemiluminescentcompoundsRequiredPhotoncounting≈5pg/mL(4)66Fluidchip67Proteinchips68Chips69Chips70臨床免疫技術(shù)的基本要素精密度（EP5）正確度檢測線性范圍（EP6)

靈敏度特異性結(jié)果可報告范圍生物參考區(qū)間(C28)

試劑穩(wěn)定性71臨床免疫技術(shù)的基本要素精密度：在規(guī)定條件下，獨立測試結(jié)果間的一致程度。（1）與真值或規(guī)定值無關(guān)；（2）以標(biāo)準(zhǔn)差表示。正確度：有大量測試結(jié)果得到的平均數(shù)與接受參照值間的一致程度。以偏倚（測試結(jié)果的期望與接受參照值之差）表示。檢測線性范圍：

靈敏度：測量儀器響應(yīng)的變化除以對應(yīng)的激勵變化。又指校準(zhǔn)曲線的斜率及對于規(guī)定量的變化分析程序產(chǎn)生信號的變化。特異性：分析方法只確定分析物，而對其他相關(guān)物質(zhì)不起作用的能力。結(jié)果可報告范圍：測量儀器的誤差處在規(guī)定極限內(nèi)的一組被測量的值。生物參考區(qū)間：通常指95%的正常人某指標(biāo)所在區(qū)間。

試劑穩(wěn)定性72臨床免疫技術(shù)的質(zhì)量控制分析前分析中分析后73臨床免疫技術(shù)的影響因素CHCH+M:Cross-reaction（交叉反應(yīng)）

Hookeffect（鉤狀效應(yīng)）

Carry-over（攜帶污染）

HAMA（異嗜性抗體）

Matrixeffect（基質(zhì)效應(yīng)） （RF、溶血、脂血、黃疸、藥物）74五、臨床應(yīng)用相關(guān)進(jìn)展75臨床應(yīng)用篩查（Screening）檢測（Detection）診斷（Diagnosis）危險性分層（Riskstratification）預(yù)后（Prognosis）監(jiān)測（Monitoring）復(fù)發(fā)（Recurrence)

預(yù)測（Prediction)篩查（Screening）Hp抗體:陰性低值(<3U/mL),陰性高值(3–10U/mL),陽性低值(10–50U/mL),陽性高值(>50U/mL).PG(+):PGI≤70ng/mL和PGI/II≤3分四組：A[Hp(?)PG(?)],B[Hp(+)PG(?)],C[Hp(+)PG(+)],D[Hp(?)PG(+)]胃癌危險性：D>C>B>AA組陰性高值者（清除感染）易出現(xiàn)小腸型腫瘤B組陽性高值者（活動性感染）易出現(xiàn)彌漫型腫瘤C組陽性低值者（晚期萎縮性）易出現(xiàn)小腸型腫瘤建議：ABC三組的隨訪監(jiān)測（胃鏡）時間分別為3、2、1年HelicobacterpyloriAntibodyTiterandGastricCancerScreeningKishikawaH,DiseaseMarkers2015,/10.1155/2015/156719方法結(jié)果篩查（Screening）德國380直結(jié)腸癌患者和2005-2013做直腸鏡的6826患者Luminex檢測64種自身抗體（根據(jù)文獻(xiàn)報道），分二步：Trainingsetandvalidationset抗MAGEA4對早期直結(jié)腸癌和晚期腺癌有較高敏感性多種自身抗體組合檢測可提高檢測的敏感性，但會降低特異性在validationset,聯(lián)合檢測抗TP53,抗IMPDH2,抗MDM2和抗MAGEA4對早期直結(jié)腸癌的敏感性為26%(95%CI,13?45%)、特異性90%(95%CI,83?94%)；同時，對晚期腺癌的檢出率也達(dá)20%(95%CI,13?29%)。Prospectiveevaluationof64serumautoantibodiesasbiomarkersforearlydetectionofcolorectalcancerinatruescreeningsettingChenH,Ondotarget2016,DOI:10.18632/oncotarget.7500方法結(jié)果81檢測（Detection）評價肝纖維化目的：肝病進(jìn)展、失代償、肝癌、對IFN反應(yīng)間接指標(biāo)：APRItest（AST/plateletratioindex）,Fornstest,FT（FibroTest）直接指標(biāo)：typeⅣcollagen,hyaluronicacid,laminin,collagenVI,TGFβ1andmetalloproteinasesortissueinhibitorsofmetalloproteinases(TIMPs),YKL-40（agrowthfactorforfibroblastsandendothelialcells）.超聲：Ultrasound-basedtransientelastography核磁：Magneticresonanceelastography金標(biāo)準(zhǔn)：活檢Non-invasiveassessmentofliverfibrosis:Betweenprediction/preventionofoutcomesandcost-effectivenessStasiC,WorldJGastroenterol2016;22(4):1711-1720Cut-offvaluesofthefirstindirectmarkersoffibrosisinthediagnosisofsignificantfibrosisandcirrhosisELF（Theenhancedliverfibrosisscoretest）：algorithmcombininghyaluronicacid,amino-terminalpropeptideoftypeⅢcollagen,tissueinhibitorofmatrix-metaloproteinase-1andage83AutoantibodiesindifferentliverdiseasesYangZX,ZhongRQ.Clinicalbiochemistry，2012檢測（detection）84診斷（Diagnosis）制備CA19.9的單克隆抗體，并改變重鏈上糖鏈，連接中介體DIBO（dibenzocyclooctyne）在DIBO再連上標(biāo)記物DFO（89Zr4+chelatordesferrioxamine）或NIRF（nearinfraredfluorescence）或同時雙標(biāo)記活體上分析腫瘤可以定位腫瘤，判斷腫瘤邊界可以發(fā)現(xiàn)腫瘤轉(zhuǎn)移灶及淋巴結(jié)Site-specificallylabeledCA19.9-targetedimmunoconjugatesforthePET,NIRF,andmultimodalPET/NIRFimagingofpancreaticcancerHoughtonJL，PNAS2015；112（52）：15850–15855方法結(jié)果Histology(A–C,Left),autoradiography(A–C,Center),andfluorescencemicroscopy(A–C,Right)ofresectedtumortissuefrommiceinjectedwith89Zr-ssdual-5B1.(A)ABxPC3xenograft,(B)metastaticfocifromamousewithaSuit-2orthotopicxenograft,and(C)theprimarytumorwithsurroundinghealthypancreastissuefromthesamemouseareshown,confirmingcolocalizationofthetracerwithCA19.9expression.(AandB)SerialNIRFimagingusingssFL-5B1(50μg)(A)and89Zr-ssdual-5B1(50μg,92±14μCi)(B).NIRFimagesofarepresentativemousefromeachcohort(n=3)bearingCA19.9-negative(T?,leftflank)andCA19.9-positive(T+,rightflank)tumorsthatwereacquiredat48hand120hareshown.Thescaleofthefluorescencesignalisreportedasradiantefficiency[(p/s/cm2/sr)/(μW/cm2)].PET,PET/CT,andNIRFimagingof89Zr-ssdual-5B1(50μg,84±6μCi)inanorthotopicPDACmodel.(A)Slices(Top,coronal;Bottom,transverse)ofarepresentativemouseat120hp.i.showhighuptakeintheprimarytumor,ametastasis,andsentinellymphnodes(LN,lymphnode;M,metastasis;T,tumor).(B)ArenderingofthePET/CTdataallowsfortheanatomizationofthelesions.(CandD)NIRFimagingofthesentinellymphnodes(C)andtheopenthoraciccavity(D)afterremovaloftheLNsdemonstratesthepotentialof89Zr-ssdual-5B1inanintraoperativesetting.87診斷（Diagnosis）自身免疫性肝炎診斷標(biāo)準(zhǔn)（IAIHG,2008）變量臨界值評分ANA或SMA1:401ANA或SMA1:802（自身抗體的附加分值最大值為2）或LKM1:40或SLA陽性IgG>正常范圍上界1>正常范圍上界1.10倍2肝臟組織（肝炎證據(jù)是必需條件）與AIH相似1典型AIH2非病毒性肝炎是26分：可能是AIH7分或以上：確定為AIH88診斷（Diagnosis）關(guān)節(jié)受累1個大關(guān)節(jié)

0分2-10個大關(guān)節(jié)

1分1-3個小關(guān)節(jié)（無論大關(guān)節(jié)受累與否）

2分4-10個小關(guān)節(jié)（無論大關(guān)節(jié)受累與否）3分>10個關(guān)節(jié)（至少1個為小關(guān)節(jié)）5分血清學(xué)RF或抗CCP抗體均陰性

0分RF或抗CCP抗體至少1項低滴度陽性（高于正常人上限水平且低于3倍正常人上限水平）

2分RF或抗CCP抗體至少1項高滴度陽性（高于3倍正常人上限水平）3分急性時相

反應(yīng)物CRP或ESR均正常0分CRP或ESR增高1分癥狀持續(xù)時間<6周0分

≥6周1分6分或以上歐洲和美國風(fēng)濕病學(xué)會的RA診斷標(biāo)準(zhǔn)（2010）89診斷（Diagnosis）臨床標(biāo)準(zhǔn)1.急性皮膚狼瘡 2.慢性皮膚狼瘡3.口腔潰瘍4.非疤痕性脫發(fā)5.2個以上關(guān)節(jié)炎 6.漿膜炎（胸膜炎或心包炎）7.神經(jīng)（癲癇或精神?。?.腎臟（尿蛋白/肌酐比值，尿蛋白>0.5g/24h或紅細(xì)胞管型）9.溶血性貧血10.白細(xì)胞減少癥（<4000/ml）1次或淋巴細(xì)胞減少癥（<1000/ml）1次11.血小板減少癥（<100000/ml）至少1次免疫學(xué)標(biāo)準(zhǔn)ANA陽性dsDNA抗體陽性（或ELISA>2倍）Sm抗體陽性磷脂抗體陽性(狼瘡抗凝物、或梅毒血清試驗假陽性、或中高滴度心磷脂抗體（IgA、IgG或IgM）、或抗β2糖蛋白I（IgA、IgG或IgM）陽性）補(bǔ)體下降（C3、C4、CH50）直接Coombs試驗陽性（除外溶血性貧血）PetriM,etal.ArthritisRheum2012;64(8):2677-26864條或以上，且各標(biāo)準(zhǔn)1條SLE診斷標(biāo)準(zhǔn)（2012，SLICC）Riskstratificationinnon-STelevationacutecoronarysyndromes:Riskscores,biomarkersandclinicaljudgment危險性分層（Riskstratification）CorcoranD，IntJCardiolHeartVasc2015;8:131-137hs-cTn：99百分位的不精密度≤10%，并在≥95%正常人中可檢測出99百分位以下的cTn濃度ESC定義MI：就診時hs-cTn陰性或接近URL，3小時內(nèi)50%變化值或絕對值升高7ng/L；就診時hs-cTn已升高，3小時內(nèi)20%變化值候選標(biāo)志物：H-FABP，CRP（系統(tǒng)性炎癥），BNP（左心功能不全），copeptin，缺血修飾的白蛋白ECG仍是一線檢查，特異性達(dá)97%，但敏感性只有28%ESCrapidrule-outofACSwithhs-cTnalgorithmESCdecision-makingalgorithminACSRenaldiseaseinscleroderma:anupdateonevaluation,riskstratification,pathogenesisandmanagement危險性分層（Riskstratification）ShanmugamVK，CurrOpinRheumatol2012；24(6):669–676彌漫型硬皮病有10%發(fā)展成硬皮病腎危象(SRC)，后者有很高的死亡率抗RNA多聚酶III：陽性時，25%進(jìn)展為SRC；陰性時只有2%；在SRC的檢出率為9.4-59%抗SCL70和抗U3RNP不是危險因素，抗著絲點抗體則呈負(fù)相關(guān)早期用類皮質(zhì)激素是危險因素（前六月每天≥15mg）HLADRB1*0407andHLADRB1*1304為獨立危險因素不是危險因素的還有：基礎(chǔ)血壓、血清肌酐、蛋白尿、血尿預(yù)后（Prognosis）

ElevatedIgG4inpatientcirculationisassociatedwiththeriskofdiseaseprogressioninmelanomaIgG4-相關(guān)疾病：一個或多個器官或組織腫脹增大，似腫瘤；IgG4陽性淋巴細(xì)胞大量增生而導(dǎo)致淋巴細(xì)胞增生性浸潤和硬化；血清IgG4細(xì)胞水平顯著增高（>1350mg/L），IgG4陽性淋巴細(xì)胞在組織中浸潤（IgG4陽性淋巴細(xì)胞占淋巴細(xì)胞的50%以上）；對糖皮質(zhì)激素治療反應(yīng)良好IgG4升高見于多種腫瘤：胰腺癌、膽管癌、鱗癌、黑色素瘤等KaragiannisP,Oncoimmunol2015/10.1080/2162402X.2015.1032492Experimentalstudydesign,collectionandprocessingofclinicalsamples.Cohortsof171melanomapatientsand104healthyvolunteerswereidentifiedforevaluationsofIgG4.IgGsubclasslevelsweremeasuredusingastandardizedLuminexbeadarrayassay(n=171).CirculatingIgG4(IgG4/IgG4total)serumlevelsinmelanomapatients(n=167)weresignificantly(P=0.007)highervs.IgG4levelsinhealthyvolunteersera(n=104).StatisticalanalysiswasperformedbyMann-WhitneyU-Test;linesrepresentmediansanderrorbarsindicateinterquartilerange.SerumIgGsubclasslevels(ng/mL)forpatientsandhealthyvolunteercohortsareshowninmiddleandright,respectively.BasedonROCanalysis,athresholdvalueof0.034forIgG4wasusedtocomparepatientserumIgG4fortheriskofprogression-freesurvival(PFS)andoverallsurvival(OS).Kaplan-MeierCurveevaluationsrevealedstatisticallysignificantlyworsePFS(HR95%[CI]2.01(1.34–3.35);log-rankP=0.0016)andlowerOS(HR95%[CI]1.90(1.17–3.29);log-rankP=0.0116)observedintheIgG4highgroupcomparedto