血清细胞因子水平监测在托珠单抗治疗幼年特发性关节炎全身型疗效评价中的应用  

The role of serum cytokine level in the evaluation of the efficacy of tocilizumab for the treatment of systemic-onset juvenile idiopathic arthritis

作　　者：苏改秀[1] 黄小兰[2] 周志轩[1] 吴凤岐[1] 赖建铭[1] Su Gaixiu;Huang Xiaolan;Zhou Zhixuan;Wu Fengqi;Lai Jianming(Division of Paediatric Rheumatology and Immunology,Capital Institute of Paediatrics,Beijing 100020,China;Central Laboratory for Clinical Research,Capital Institute of Paediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院风湿免疫科,北京100020 [2]首都儿科研究所附属儿童医院中心实验室,北京100020

出　　处：《中华检验医学杂志》2020年第1期85-90,共6页Chinese Journal of Laboratory Medicine

摘　　要：目的探讨血清细胞因子水平对评价托珠单抗治疗幼年特发性关节炎全身型(systemic-onset juvenile idiopathic arthritis,SoJIA)疗效的意义。方法选取2016年6月至2018年10月在首都儿科研究所附属儿童医院住院的SoJIA患儿30例,其中男20例(67%),女10例(33%),诊断时年龄为0.84至13岁。使用白细胞介素-6受体拮抗剂(托珠单抗注射液)治疗,观察治疗前、用药2周后、用药6周后及用药22周后的血白细胞(WBC)、C反应蛋白(CRP)、动态红细胞沉降率(AESR)、血清白细胞介素(IL-6、IL-2R、IL-8、IL-10、IL-1β)及肿瘤坏死因子α(TNF-α)水平。采用Mann-Whitney非参数检验以及卡方检验分析用药后不同时间上述细胞因子水平的差异。结果30例患儿,用药前均有发热,其中28例患儿应用托珠单抗后体温降至正常,治疗期间未再出现发热,1例患儿用药后出现过敏反应后停药,1例用药后疗效不佳停药。在用药后体温正常的28例患儿中,其关节炎及皮疹表现均有明显改善,且WBC、AESR及CRP均较用药前下降。28例SoJIA患儿,血清IL-6水平在第2周为107.50(28.03~281.50)pg/mL,与治疗前[168.50(67.40~589.25)pg/mL]相比差异无统计学意义(Z值为-1.754,P>0.05),用药6周后为64.05(19.90~130.75)pg/mL,用药22周后为24.80(3.45~95.40)pg/mL,浓度均低于治疗前,差异有统计学意义(Z值分别为-2.942、-3.334,P值均为<0.01);血清IL-2R水平第2周为740.50(510.00~1161.00)U/mL,第6周为796.50(534.00~1008.00)U/mL,第22周为688.00(527.00~889.50)U/mL,分别与治疗前[1322.50(812.00~1659.00)U/mL]相比,均低于治疗前水平,差异有统计学意义(Z值分别为-2.818、-3.130、-3.466,P值均<0.01);TNF-α浓度在用药2周后为23.70(20.30~41.23)pg/ml,6周后为26.75(16.83~47.03)pg/ml,22周后为18.60(13.10~34.90)pg/ml,分别与治疗前的26.50(20.55~37.43)pg/ml比较差异无统计学意义(Z值分别为0、-0.560、-1.954,P值均>0.05);IL-8浓度在用药2周后为200.85(95.43~364.00)pg/ml,6周后为194.50(50.7Objective To evaluate the value of serum cytokine level in the efficacy of tocilizumab for the treatment of systemic-onset juvenile idiopathic arthritis.Methods 30 cases with SoJIA hospitalized in Capital Institute of Paediatrics from June 2016 to October 2018 were treated with Interleukin-6 receptor antagonist(tocilizumab)injection.Among them,20 were males(67%)and 10 were females(33%).The age at diagnosis was between 0.84 to 13years.Whiteblood cell,C-reactive protein,erythrocyte sedimentation rate,serum interleukin(IL-6,IL-2R,IL-8,IL-10,IL-1β)and tumor necrosis factor-alpha levels were observed before treatment,after the 2nd week,after the 6th week and after the 22nd week.Mann-Whitney nonparametric test and Chi-square test were used to analyze the data of cytokines pre and after-treatment.Results All of the 30 cases had fever before medication.The fever disappeared in 28 cases after using tocilizumab.One case stopped using tocilizumab because of allergic reaction and one case stopped because of poor efficacy.Among 28 cases with normal body temperature after medication,the arthritis and rash manifestations were significantly improved.WBC,AESR and CRP were all lower than those before medication.Within these 28 cases,the serum IL-6 level was168.50(67.40-589.25)pg/mL pre-treatment,107.50(28.03-281.50)pg/mL after the 2nd week.There was no statistical difference between them(Z=-1.754,P>0.05).The serum IL-6 level was 64.05(19.90-130.75)pg/mL after the 6th week and 24.80(3.45-95.40)pg/mL after the 22nd week.Compared with pre-treatment,they were all lower than pre-treatment levels(Z=-2.942,-3.334,P<0.01,<0.01).Serum IL-2R level was 740.50(510.00-1161.00)U/mL after the 2nd week,796.50(534.00-1008.00)U/mL after the 6th week and 688.00(527.00-889.50)U/mL after the 22nd week.Compared with pre-treatment[1322.50(812.00-1659.00)U/mL],they were all lower than pre-treatment levels(Z=-2.818,-3.130,-3.466,P<0.01,<0.01,<0.01).Serum TNF-alpha level was 23.70(20.30-41.23)pg/ml after the 2nd week,26.75(16.83-47.03)pg/ml after the 6th

关 键 词：细胞因子 托珠单抗 幼年特发性关节炎全身型 

分 类 号：R72[医药卫生—儿科]