肠道病毒71型重症手足口病患儿脑脊液IgM抗体测定的临床意义

Detection of cerebrospinal fluid anti-enterovirus 71 IgM in children with severe hand, food and mouth disease induced by enterovirus 71 infection and its clinical significance

目的 测定重症手足口病（HFMD）患儿脑脊液肠道病毒71 （EV71） IgM抗体水平,分析脑脊液EV71-IgM抗体、脑脊液常规和生化检查及其与临床资料关系,为EV71重症HFMD患儿实验室诊断提供新参考.方法 收集2014年3至6月杭州市儿童医院收治的实验室确诊为EV71型感染重症HFMD患儿294例的临床资料,其中危重型53例,重型241例;酶联免疫吸附方法测定脑脊液EV71-IgM,并进行脑脊液常规和生化检测,结合临床资料进行统计分析;选取同期住院确诊为其他肠道病毒型感染重症HFMD患儿41例做抗体对照检测.结果 294例实验室确诊EV71感染重症HFMD患儿脑脊液EV71-IgM抗体总阳性率为60.2％ （177/294）,其中危重型阳性率62.3％ （33/53）,重型阳性率59.8％（144/241）,41例对照组脑脊液EV71-IgM抗体均阴性.脑脊液EV71-IgM抗体阳性组的年龄[（2.5±1.2）岁]小于阴性组[（2.9±1.1）岁],差异有统计学意义（t=2.595,P=0.010）,且在脑脊液EV71-IgM抗体阳性组中,危重型患儿年龄[（1.9±0.7）岁]与重型患儿年龄[（2.6±1.2）岁]比较,差异有统计学意义（t =3.150,P=0.002）.抗体阳性组脑脊液有核细胞计数及阳性率[105（56,180）×106/L; 97.7％ （173/177）]均高于抗体阴性组[62（30,150）× 106/L;83.8％（98/117）],两组比较差异均有统计学意义（Z=3.663,P=0.000;x2=19.089,P=0.000）,抗体阳性组以单核细胞为主[（57±25）％],抗体阴性组细胞分类单核细胞与多核细胞比例相当[（50±26）％比（50±26）％],抗体阳性组与阴性组相比,差异有统计学意义（t=2.343,P=0.020）.脑脊液抗体阳性患儿中,危重型患儿脑脊液有核细胞数＞ 100×106/L比例占69.7％（23/33）,与重型患儿比例47.2％ （68/144）比较差异有统计学意义（x2=5.429,P=0.02）;脑脊液蛋白质定量及阳性率抗体阳性组均高于阴性组,比较差异均有统计学意义（Z =2.158,P=0.031;x2=5.921,P=0.015）.结论 脑脊液EV71-IgM抗体测定可成为重症HFMD患儿实验室检查的重要指标,EV71-IgM抗体结果与脑脊液有核细胞计数与分类及蛋白质浓度相关.脑脊液抗体阳性患儿,有核细胞计数越高,年龄越小,越容易向危重型发展.

Objective To detect the anti-enterovirus 71 （EV71） IgM level in cerebrospinal fluid （CSF） of children with severe hand,foot and mouth disease （HFMD） induced by EV71 and then analyze the relationships among the IgM antibody levels,CSF routine examination and patients＆#39; clinical features,and thus to evaluate the clinical significance of anti-EV71 IgM as a new indicator for early diagnosis of children with severe HFMD induced by EV71.Method A total of 294 laboratory-confirmed cases of children with severe HFMD infected with EV71 were enrolled into the research group from March 2014 to June 2014,consisting of 53 fatal cases and 241 severe cases,and their CSF samples underwent enzyme-linked immunosorbent assay （ELISA） for anti-EV71 IgM levels,CSF routine and biochemical tests.Forty-one cases of children with severe HFMD induced by other enteroviruses were collected as antibody-testing control group during the same period.Result In the research group,the total positive rate of anti-EV71 IgM in 294 CSF samples of children with severe HFMD infected by EV71 was 60.2% （177/294） ; the positive rate of anti-EV71 IgM in the fatal HFMD subgroup was 62.3% （33/53） ; the positive rate of anti-EV71 IgM in the severe HFMD subgroup was 59.8% （144/241）.In the control group,the results of CSF anti-EV71 IgM tests were all negative （0/41）.In the research group,patients in antibody-positive subgroup（2.5 ± 1.2） years old were younger than those in antibody-negative subgroup （2.9 ± 1.1） years old （t =2.595,P =0.010）.And within the antibody-positive subgroup,the patients （（1.9 ±0.7） years old） with fatal type disease were younger than those （（2.6 ± 1.2） years old） with severe type disease （t =3.150,P =0.002）.The CSF nucleated cells count and positive rates（105（56,180） × 106/L;97.7% （173/177）） in antibody-positive subgroup were higher than those （62（30,150） × 106/L;83.8% （98/117）） in antibody-negative subgroup （Z =3.663,P =0.000 ; x2 =19.089,P =0.000）.In antibody-positive subgroup,the percentage of monocytes （57 ± 25） % was higher than that of polykaryocytes （43 ± 25） %.In antibody-negative subgroup,the percentage of monocytes （50 ± 26）% was close to that of polykaryocytes （50 ± 26）%.In the antibody-positive subgroup,the ratio of the patients with nucleated cells count higher than 100 × 106/L in fatal type group and severe type group was 69.7% （23/33） and 47.2% （68/144） respectively （x2 =5.429,P =0.02）.The CSF protein quantity and positive rates in antibody-positive subgroup were higher than those in antibody-negative subgroup （Z =2.158,P =0.031 ; x2 =5.921,P =0.015）.Conclusion The anti-EV71 IgM levels in CSF can serve as an important indicator for early diagnosis of children with severe HFMD induced by EV71.And the anti-EV71 IgM levels in CSF correlated to the CSF nucleated cells count and classification and CSF protein quantity.In the antibody-positive subgroup,the higher the nucleated cell count or the younger the age,the higher the possibility of patients to develop into fatal cases.