调节性B细胞和调节性T细胞与英夫利昔单抗治疗克罗恩病临床疗效的关系  

Association of Breg cells and Treg cells with the clinical effects of Infliximab in the treatment of Chinese patients with Crohn′s disease

作　　者：林芊如 夏宣平[1] 蔡小鸟 胡定元[1] 邵晓晓[1] 夏盛隆[1] 蒋益[1] Lin Qianru;Xia Xuanping;Cai Xiaoniao;Hu Dingyuan;Shao Xiaoxiao;Xia Shenglong;Jiang Yi(Department of Gastroenterology,Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院消化内科,温州325000

出　　处：《中华医学杂志》2020年第42期3303-3308,共6页National Medical Journal of China

基　　金：浙江省自然科学基金(LY16H160055,LY17H030011);温州市科技计划项目(Y20150029,Y20160102,Y20170062,Y20170637)。

摘　　要：目的探讨外周血调节性B细胞(Breg细胞)和调节性T细胞(Treg细胞)与英夫利昔单抗治疗克罗恩病临床疗效的关系。方法2017年1月至2019年6月期间,在温州医科大学附属第二医院收集32例活动期克罗恩病患者和33名性别、年龄相匹配的健康对照者。取空腹静脉血5 ml,分离外周血单个核细胞(PBMCs),经多色流式细胞术检测PBMCs中Breg细胞(CD3-CD19^+IL-10^+B细胞)占B细胞的比例,以及Treg细胞(CD4^+CD25^+Foxp3^+T细胞)占CD4^+T细胞的比例。克罗恩病患者于第0、2、6周静脉注射英夫利昔单抗(5 mg/kg)诱导缓解,其后每隔8周给予相同剂量的英夫利昔单抗维持治疗。于第14周再次检测PBMCs中Breg细胞比例和Treg细胞比例,并与第0周进行比较。同时,克罗恩病患者分别于第0周和第14周检测C反应蛋白(CRP)、白细胞计数、血小板计数、血细胞沉降率辅助评估英夫利昔单抗疗效。结果英夫利昔单抗治疗前,克罗恩病组与健康对照组之间整体比较,PBMCs中Breg细胞比例较高[(3.15±1.17)%比(2.64±0.38)%,P=0.024],Treg细胞比例较低[(2.15±0.49)%比(4.25±0.41)%,P<0.001]。英夫利昔单抗治疗前和治疗第14周,克罗恩病组中Breg细胞比例和Treg细胞比例均呈独立正相关(r=0.628,P<0.001;r=0.749,P<0.001)。治疗第14周,根据症状、克罗恩病活动指数(CDAI)、内镜下黏膜愈合进行评估。CDAI<150且内镜下黏膜愈合者定义为缓解组(R组),CDAI≥150或内镜下黏膜未愈合者为未缓解组(N组)。治疗第14周与治疗前比较,R组中Breg细胞比例和Treg细胞比例均显著增高[(5.89±2.60)%比(3.19±1.27)%,P<0.001;(4.59±0.72)%比(2.08±0.47)%,P<0.001],CDAI和CRP均显著降低[CDAI:(63.19±14.69)比(195.62±58.13),P<0.001;CRP:(3.65±2.23)mg/L比(29.80±30.06)mg/L,P<0.001]。治疗前和第14周,克罗恩病患者中Breg细胞比例和Treg细胞比例与CRP(r=-0.279,P=0.026;r=-0.406,P=0.001)和CDAI(r=-0.409,P=0.001;r=-0.708,P<0.001)始终呈独立负相关。治疗第Objective To explore the associations of regulatory B cells(Breg cells)and regulatory T cells(Treg cells)with the clinical effect of Infliximab in the treatment of Chinese patients with Crohn′s disease(CD).Methods From January 2017 to June 2019,a total of 32 CD patients at active stage and 33 age and gender-matched healthy controls were collected from the Second Affiliated Hospital of Wenzhou Medical University in this study.Approximate 5 ml of peripheral fasting venous blood was obtained from every subject.Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood.Then multi-color flow cytometry was applied to determine the proportion of Breg(CD3-CD19^+IL-10^+B cells)in B cells and the proportion of Treg(CD4^+CD25^+Foxp3^+T cells)in CD4^+T cells.Infliximab(5 mg/kg)was given intravenously at week 0,2 and 6 to induce CD remission,and then maintained with the same dose of Infliximab every 8 weeks.And the proportions of Breg and Treg were examined at week 14 of Infliximab treatment,then compared with those of week 0.Simultaneously,C-reactive protein(CRP),leucocyte count,platelet count,erythrocyte sedimentation rate were detected in CD patients to assess the clinical effect at week 0 and 14 of Infliximab treatment.Results Before infliximab treatment,compared with healthy controls,the proportion of Breg in B cells was significantly increased[(3.15±1.17)%vs(2.64±0.38)%,P=0.024)],and the proportion of Treg in CD4^+T cells was significantly decreased[(2.15±0.49)%vs(4.25±0.41)%,P<0.001]in CD patients.And the proportion of Breg was positively related with the proportion of Treg in CD patients either at week 0 or week 14 of Infliximab treatment(r=0.628,P<0.001;r=0.749,P<0.001).At week 14 of Infliximab treatment,according to symptoms,Crohn′s disease activity index(CDAI)and endoscopic mucosal healing,CD patients were classified as remission group(CDAI<150 and endoscopic mucosal healing,R group)and non-remission group(CDAI≥150 or mucosal non-healing group,N group).Compared with CD patients at week 0 of I

关 键 词：CROHN病 调节性B细胞 调节性T细胞 英夫利昔单抗 

分 类 号：R574.62[医药卫生—消化系统]