早期诊断和监测系统性红斑狼疮患儿活动性人类巨细胞病毒感染的研究

Early diagnosis and monitoring of active human cytomegalovirus infection in children with systemic lupus erythematosus

目的 了解系统性红斑狼疮 (systemiclupuserythematosus,SLE)患儿活动性人类巨细胞病毒 (humancytomegalovirus,HCMV)感染的状况 ,并比较不同实验室检测方法的诊断价值。方法 实验组观察了 2 1例初诊为SLE并接受免疫抑制治疗的患儿 ,对照组观察了 2 1例免疫力正常的骨科患儿。治疗前后应用间接免疫荧光法检测外周血多形核白细胞 (polymorphonuclearleukocytes,PMNLs)中的HCMVpp6 5抗原和p72抗原 ,PCR方法检测血清中的HCMVDNA ,ELISA方法检测血清中的HCMVIgM和IgG抗体。结果 实验组活动性HCMV感染发生率为 2 9% (6 /2 1) ,4例发生于免疫抑制治疗后 ,另外 2例发生于免疫抑制治疗前 ,对照组无 1例发生活动性感染 ,两组相比差异有显著性(P =0 0 2 7)。实验组各项实验室检测的阳性率分别为 :pp6 5 2 4% (5 /2 1)、p72 14% (3/2 1)、DNA 43 % (9/2 1)、IgM 10 % (2 /2 1)、IgG 91% (19/2 1)。实验组各项实验室检测方法诊断活动性HCMV感染的敏感性分别为 :pp6 5 83% (5 /6 )、p72 5 0 % (3/6 )、DNA 10 0 % (6 /6 )、IgM 33% (2 /6 )、IgG(双份血清抗体滴度呈≥ 4倍增高 ) 5 0 % (3/6 )。特异性除PCR方法为 80 % (12 /15 )外 ,其余均为 10 0 % (15 /15 )。

Objective Human cytomegalovirus (HCMV) is one of the most important opportunistic pathogens and frequently causes severe and life threatening diseases in immunocompromised individuals who are mainly transplant recipients and patients with AIDS according to previously published reports. Patients with systemic lupus erythematosus (SLE) are at high risk for developing active HCMV infections due to immunodepression caused by SLE itself and immunosuppressive therapy, but there have been very few comprehensive studies on this topic, especially in pediatric cases. The purpose of this prospective study was to investigate the prevalence and features of active HCMV infection in children with SLE and evaluate the diagnostic value of the HCMV antigenemia assay, PCR, and serological tests. Methods Twenty one SLE children who underwent immunosuppressive therapy were enrolled in this study. As a control group, twenty one immunocompetent children with skeletal malformation were also involved in this study. The 2 groups were comparable in age (range, 8 13 years), sex, and observation period. Serum and whole blood samples were collected before and monthly after immunosuppression during a successive 2 to 3 month period. Immunofluorescence assay, PCR, and serological tests were used to determine HCMV pp65 and p72 antigen in leukocyte, HCMV DNA in sera, and HCMV specific IgM and IgG antibodies, respectively. Results Active HCMV infection was diagnosed in 29% (6/21) of SLE patients, while none in control group. The difference between two groups was significant ( P =0 027). Two out of 6 SLE patients developed active HCMV infection before immunosuppressive therapy and the other 4 patients developed after immunosuppressive therapy. Among the 21 SLE children, HCMV pp65 antigenemia was detected in 5 patients, p72 antigenemia in 3 patients, HCMV DNA in sera in 9 patients, serum HCMV specific IgM in 2 patients, and IgG in 19 patients. The sensitivity and specificity for diagnosis of active HCMV infection were 83%, 100%, respectively for pp65 antigenemia; 50%, 100% for p72 antigenemia; 100%, 80% for serum PCR; 33%, 100% for serum HCMV IgM antibody detection and 50%, 100% for serum HCMV IgG antibody detection.Conclusion Compared with control group, the active HCMV infection seemed to be a much more common complication in SLE children. It could occur before treatment with immunosuppressive agents, but mostly occurred after immunosuppressive therapy. Compared with other techniques used in this study, the pp65 antigenemia assay seemed to be a better method for the early diagnosis and monitoring of active HCMV infection in children with SLE.