外周血NK细胞百分数与肉芽性多血管炎的
作者：MerktW翻译：姚中强
摘要引言:天然杀伤细胞CD3-CD56+(NK)细胞在肉芽肿性多动脉炎(GPA)中的作用不明。近来，有研究表明NK细胞可以杀伤肾脏微血管内皮细胞，提示NK细胞在这类疾病中有致病性。目前尚未阐明亚型分布、表型和外周血NK细胞功能与肉芽肿性多动脉炎疾病活动性的相关性。而且，尚不知NK细胞是否浸润肉芽肿性多动脉炎组织损害处。
方法:使用抗CD56抗体和抗CD3抗体染色石蜡包埋的肉芽肿性多动脉炎肉芽肿和对照组组织切片。流式细胞术分析外周血淋巴细胞亚群。使用患者外周血单个核细胞和靶细胞共培养及细胞表面CDa表达来分析NK细胞脱颗粒。从病历中提取临床数据。探索性方式进行统计分析。
结果:活动性肉芽肿性多动脉炎患者病损处无CD56+细胞，但可见于结核和结节病肉芽肿处。在肉芽肿性多动脉炎中，外周血淋巴细胞中的NK细胞百分数与伯明翰血管炎活动性积分(BVAS)负相关(n?=?28)。相应地，NK细胞百分数与缓解持续时间正相关(n?=?28)，病情不活动的肉芽肿性多动脉炎(BVAS?=?0,n?=?17)患者中的NK细胞百分数高于病情活动患者、健康对照(n?=?29)和病情不活动的对照疾病(n?=?12)。长时间缓解和免疫抑制剂减量患者的NK百分数最高。外周血淋巴细胞(n?=?12/28)中NK细胞百分数18.5%可确定肉芽肿性多动脉炎病情不活动，特异性高达%。无论其病情是否活动，肉芽肿性多动脉炎患者分化为CD56弱和CD56亮的NK细胞亚型无变化(n?=?28)。也确定了活化NK细胞受体(NKp30、NKp46和NKG2D)细胞表面的表达类似。与健康对照一样，肉芽肿性多动脉炎患者的NK细胞在同时存在NK细胞受体的上皮和淋巴靶细胞时进行脱颗粒。
结论:肉芽肿性多动脉炎肉芽肿病变中检测不到NK细胞。外周血NK细胞百分数与肉芽肿性多动脉炎病情不活动正相关，可作为疾病活动标志物。肉芽肿性多动脉炎患者外周血NK细胞为成熟NK细胞，保留了其免疫识别功能。
附原文：AbstractINTRODUCTIONTheroleofCD3-CD56+naturalkiller(NK)cellsingranulomatosiswithpolyangiitis(GPA)ispoorlyunderstood.Recently,ithasbeenshownthatperipheralbloodNKcellscankillrenalmicrovascularendothelialcells,suggestingapathogenicroleofNKcellsinthisdisease.Sofar,subsetdistribution,phenotype,andfunctionofperipheralbloodNKcellsinrelationtoGPAdiseaseactivityhavenotbeenelucidated.Moreover,itisnotknownwhetherNKcellsinfiltrateGPAtissuelesions.METHODSParaffinsectionsofGPAgranulomasandcontrolswerestainedwithanti-CD56andanti-CD3antibodies.Peripheralbloodlymphocytesubsetswereanalyzedbyflowcytometry.NKcelldegranulationwasanalyzedusingcoculturesofpatientPBMCswithtargetcellsandsurfaceexpressionofCDa.Clinicaldatawereextractedfrommedicalrecords.Statisticalanalysiswasperformedinanexploratoryway.RESULTSCD56+cellswerenotdetectableinactivegranulomatousGPAlesionsbutwerefoundfrequentlyingranulomasfromtuberculosisandsarcoidosispatients.InGPA,theproportionofNKcellsamongperipheralbloodlymphocytescorrelatednegativelywiththeBirminghamVasculitisActivityScore(BVAS)(n?=?28).Accordingly,NKcellpercentagescorrelatedpositivelywiththedurationofremission(n?=?28)andweresignificantlyhigherininactiveGPA(BVAS?=?0,n?=?17)thaninactiveGPA,healthycontrols(n?=?29),andinactivecontroldiseases(n?=?12).ThehighestNKcellpercentageswerefoundinpatientswithlong-termremissionandtaperedimmunosuppressivetherapy.NKcellpercentages18.5%ofperipheralbloodlymphocytes(n?=?12/28)determinedGPAinactivitywithaspecificityof%.ThedifferentiationintoCD56(dim)andCD56(bright)NKcellsubsetswasunchangedinGPA(n?=?28),irrespectiveofdiseaseactivity.SimilarsurfaceexpressionoftheactivatingNKcell-receptors(NKp30,NKp46,andNKG2D)wasdetermined.Likeinhealthycontrols,GPANKcellsdegranulatedinthepresenceofNKcellreceptorligandbearingepithelialandlymphatictargetcells.CONCLUSIONSNKcellswerenotdetectableinGPAgranulomas.PeripheralbloodNKcellpercentagespositivelycorrelatewiththesuppressionofGPAactivityandcouldserveasabiomarkerforGPAactivity.PeripheralbloodNKcellsinGPApatientsarematureNKcellswithpreservedimmunerecognition.
引自：MerktW,SturmP,LasitschkaF,TretterT,WatzlC,SaureD,HundemerM,SchwengerV,BlankN,LorenzHM,CerwenkaA.Peripheralbloodnaturalkillercellpercentagesingranulomatosiswithpolyangiitiscorrelatewithdiseaseinactivityandstage.ArthritisResTher.Nov21;17(1):.doi:10./s---7.
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