膝关节骨关节炎中英文合并版PPT课件.ppt

NewToolsforIdentifyingInflammatoryandOsteoarthritisPhenotypes VirginiaByersKraus MD PhDProfessorofMedicine医学教授DukeUniversitySchoolofMedicine杜克大学医学院DukeInstituteforMolecularPhysiology杜克分子生理研究所Durham NCSeptember2013 识别炎症与骨关节炎表型的新工具 HistoryofOsteoarthritis FromthetimesofHippocratesallformsofchronicarthritiswereregardedasmanifestationsofgout DequekerandLuyten 2008 AnnRheumDis 67 5 10 SirArchibaldGarrodcoinedtheterm osteoarthritis OA in1890 Debatehasragedeversince isOAamechanical non inflammatory oraninflammatorydisease 1890年 ArchibaldGarrod爵士提出了 骨关节 Osteoarthritis OA 这个名词 争论一直持续至今 OA究竟是一种机械性 非炎症 或是一种炎症性疾病 骨关节炎的历史 从希波克拉底时期 所有形式的慢性关节炎都被认为是痛风的表现 HistoryofOsteoarthritis骨关节炎的历史 OsteoarthritisisBOTHamechanicalandaninflammatorydisease 骨关节炎既是一种机械性疾病也是一种炎症性疾病 WhyHasitTakenSoLongtoRecognizethatOsteoarthritisisanInflammatoryDisease NORMALCARTILAGE正常软骨 Thenon vascularizeddamagedcartilagecannotrespondbyausualinflammatoryresponse 无血管损伤后的软骨不能应答正常的炎症反应 为什么人们花了这么久才认识到骨关节炎是一种炎症性疾病 SignsofInflammationinOsteoarthritisareFrequentWhenSensitiveToolsareUsed Frequenteffusions频繁关节积液Song2008 78 byultrasoundand81 byMRIin超声检测78 和MRI检测81 Tarhan2003 70 byultrasound 80 byMRI超声检测70 和MRI检测80 Frequentsynovialthickening频繁滑膜增厚Tarhan2003 34 byultrasound 50 byMRI超声检测34 和MRI检测50 Frequentpopliteal Baker s cysts频繁腘窝囊肿 Baker囊肿 Tarhan2003 40 byultrasound 35 byMRI超声检测40 和MRI检测35 References参考文献 Songetal AnnRheumDis2008 67 1 19 25Tarhanetal ClinRheumatol2003 22 3 181 8 当使用一些敏感的检测手段时 骨关节炎的炎症指标就会频繁出现 SignsofInflammationinOsteoarthritisarealsoFrequentataMolecularLevel Innateimmunityistriggered先天免疫被激活HighexpressionandactivationofComplement补体激活及高表达ActivationbyCrystals Calciumpyrophosphatedihydrate basiccalciumphosphateanduricacidcrystals被晶体激活 二水焦磷酸钙化合物 碱性磷酸钙和尿酸结晶LevelsofseveralInflammatoryMediatorsarehigherinOAthanhealthyseraandsynovialfluidOA患者血清及滑夜中一些炎症介质的水平高于正常人PresenceofMacrophagesinsynovium滑膜中存在巨噬细胞 References参考文献 BerenbaumF OsteoarthritisCartilage2013 21 1 16 21Denoble Krausetal ProcNatlAcadSciUSA2011 108 5 2088 93 在分子水平上 骨关节炎的炎症指标同样也会频繁出现 SignsofInflammationinOsteoarthritiscanbeDemonstratedinvivoby99mTc EC20 FolateScans 在分子水平上 骨关节炎的炎症指标同样也会频繁出现 TheFolateReceptorisexpressedonactivatedbutnotrestingmacrophages LowPS etal AccChemRes2008 41 1 120 9 活化非静息的巨噬细胞能够表达叶酸受体Anewimagingagent 99mTc EC20 Etarfolatide canidentifyactivatedmacrophagesinvivo 一个新型成像试剂 99mTc EC20 Etarfolatide 能够识别体内活化的巨噬细胞99mTc EC20 Etarfolatide consistsofthevitaminfolateconjugatedto99mTcviaachelatingmoiety 一个新型成像试剂 99mTc EC20 Etarfolatide 能够识别体内活化的巨噬细胞 NuclearmedicineradiopharmaceuticalforIVinjection Results SPECT CT99mTc EC20IdentifiesActivatedMacrophagesinOAJoints结果 SPECT 单光子发射CT CT99mTc EC20识别OA关节内活化的巨噬细胞 SubchondralBone软骨下骨 SynovialandJointSpace 滑膜与关节腔 StudyDesignandResults研究设计及结果 25subjects 50knees 25例受试者 50例膝关节 atleastonekneewithradiographicosteoarthritiswithsymptom至少一侧膝关节有影像学OA并有症状表现KL1 24 KL2 26 KL3 32 KL4 18 KL1 24 KL2 26 KL3 32 KL4 18 72 female meanage62years meanBMI29kg m272 女性 平均年龄62岁 平均BMI29kg m276 ofkneeswerepositivefor99mTc EC20uptake76 膝关节摄取99mTc EC20为阳性99mTc EC20 especiallyinthesynovium wasassociatedwithkneesymptoms p 0 0001 99mTc EC20 特别是在滑膜中 与膝关节症状相关 p 0 0001 99mTc EC20wasassociatedwithradiographicseverityofosteoarthritis p 0 01to0 001 99mTc EC20与OA放射学严重程度相关 p 0 01to0 001 Krausetal OsteoCartilage2013 21 Supplement April S42 KL KellgrenLawrencegradeofkneeosteoarthritisseverity Synovial99mTc EC20IntensityAssociatedwithKneeSymptoms滑膜99mTc EC20强度与膝关节的症状相关 KNEES1 50 orderedbysynovial99mTc EC20uptake ZSCOREZ评分 膝关节1 50 按滑膜99mTc EC20摄取量排序 Results 99mTc EC20UptakeinOtherJointswasalsoAssociatedwithSymptoms结果 99mTc EC20的摄取量与其他关节的症状也相关 Adjustedforinter jointcorrelationwithGeneralizedEstimatingEquations UnderstandingOsteoarthritisPhenotypes KrausinspiredbyBerenbaum2013 INNATEIMMUNITY MACROPHAGES先天免疫 巨噬细胞 对骨关节炎表型的理解 NewModelofOsteoarthritisasBothaMechanicalandanInflammatoryDisease MECHANICAL机械性ExtrinsicIncitingAgents外在刺激因子Macroinjury宏观损伤Microinjury微观损伤Environment环境 IntrinsicRiskFactors固有的风险因素Age年龄Obesity肥胖Gender性别Geneticsusceptibility遗传易感性levelofrepair innateimmuneresponses修复和先天免疫应答水平 INFLAMMATION炎症Activated激活Macrophages巨噬细胞Complement补体Alarmins警报素 Kraus VB 2014 PreclinicalOsteoarthritis In Rheumatology 6thedition Ed MCHochberg AJSilman JSSmolen MEWeinblatt MHWeisman MosbyElsevier Philadelphia Chapter179 inpress 将OA作为机械性及炎症性疾病的新模型 Acknowledgments致谢 Co investigators共同研究者 GaryMcDaniel JanetLHuebner ThomasStabler CarlPieper REdwardColeman NeilAPetry PhilipSLow JaiyinShen andPeterMitchellHikmatDaghestani Funding基金赞助 Inve