【作者】 王静；

【导师】 杨丽；

【作者基本信息】 天津医科大学 ， 神经病学， 2014， 硕士

【摘要】 目的研究长节段横贯性脊髓炎(LETM)和视神经脊髓炎(NMO)患者急性期血清水通道蛋白4(AQP4)抗体的水平,分析AQP-4抗体水平与临床特征的相关性,探讨抗体水平与疾病活动性及预后的关系,寻找AQP-4抗体参与NMOSDs免疫病理机制的临床依据。方法选取特发性LETM患者72例,NMO患者78例,利用荧光免疫沉淀法(FIPA)对其急性期血清AQP-4抗体进行定量检测,回顾性分析其临床及影像学特点,采用扩展残疾状态量表(EDSS)评价病情严重程度,核磁共振(MRI)评估受累病灶,采用Spearman等级相关进行数据分析。在血清AQP-4抗体阳性的LETM患者中,研究抗体水平与急性期EDSS评分、最后一次随访时EDSS评分、脊髓受累节段数、下次复发间隔时间、转化为NMO时间等临床特征的相关性；在NMO患者中,研究抗体水平与急性期EDSS评分、脊髓受累节段数、头MRI病灶数、下次复发间隔时间等临床特征的相关性。结果1.在72例特发性LETM患者中,血清AQP-4抗体的阳性率为68%。2.在血清学AQP-4抗体阳性的LETM患者中(1)急性期EDSS评分、最后一次随访时EDSS评分、脊髓受累节段数均与血清AQP-4抗体水平呈正相关(r=0.463,P=0.001；r=0.424,P=0.003；r=0.142,P=0.039)；(2)至下次复发间隔时间及转化为NMO时间均与AQP-4抗体水平无明显相关性(r=-0.29,P=0.073；r=-0.141,P=0.458)。3.在78例NMO患者中,血清AQP-4抗体的阳性率为73.1%。4.在78例NMO患者中(1)急性期EDSS评分、脊髓受累节段数、头MRI病灶数均与血清AQP-4抗体水平呈正相关(r=0.423,P=0.0001；r=0.355,P=0.002；r=0.286,P=0.022)；(2)至下一次复发间隔时间与血清AQP-4抗体水平无明显相关性(r=-0.126,P=0.532)。结论1.在NMO患者及血清学AQP-4抗体阳性的LETM患者中,急性期EDSS评分、脊髓受累节段数与血清AQP-4抗体水平相关,提示抗体水平与NMOSD疾病的严重程度、活动性有一定相关性,提示AQP-4抗体可能参与其致病过程。2.在血清学AQP-4抗体阳性的LETM患者中,最后一次随访时的EDSS评分与血清AQP-4抗体水平相关,提示LETM初次发病时急性期的AQP-4抗体水平可以提示以后的残疾程度。3.在NMO患者中,头MRI病灶数与与血清AQP-4抗体水平相关,提示AQP-4抗体可能是形成颅内病灶的主要原因。4.在血清学AQP-4抗体阳性的LETM患者中,血清AQP-4抗体水平与下一次复发间隔时间及转化为NMO时间均无相关性,且在NMO患者中,抗体水平与下次复发间隔时间无明显相关性,提示单次急性期血清AQP-4抗体水平预测NMOSD疾病复发及转化的意义可能不大。更多还原

【Abstract】 ObjectiveTo detect the aquaporin-4(AQP-4) antibody in patients suffering from the acute longitudinally extensive transverse myelitis (LETM) and neuromyelitis optica(NMO). To investigate the correlation between AQP-4antibody titres and clinical characteristics. To analyse the association the antibody titers and disease activity and. prognosis. To provide clinical evidence for the pathogenicity of AQP-4antibody in NMOSD.MethodsTo perform quantitative detection to the sera AQP-4antibody of72idiopathic LETM and the78NMO patients in our hospital by immunofluorescent precipitation assay (FIPA). To retrospectively investigate the clinical manifestation and magnetic resonance imaging (MRI) feature. The disability severity in NMOSDs was assessed by the Expanded Disability Status Scale (EDSS). Magnetic resonance imaging (MRI) was performed to assess the involved lesions. The Spearman’s rank correlation was used as appropriate data analysis. In the seropositive LETM patients, we evaluated the correlation between AQP-4antibody titers and clinical parameters such as EDSS scores(at first episode and at last follow-up), number of segments of spinal cord involved, the interval period to next relapse and the conversion period of LETM to NMO. In patients with NMO, the correlation between AQP-4antibody titers and clinical parameters such as EDSS scores(at acute stage), number of segments of spinal cord involved and brain lesions count on MRI, the interval period to next relapse was analysed.Results1. The positivity for AQP4-Ab in patients with idiopathic LETM was68%.2.By Spearman analysis,we found that EDSS scores(at acute stage and at lastfollow-up), number of segments of spinal cord involved were positively correlated to AQP-4antibody levels (r=0.463,P=0.001; r=0.424,P=0.003;r=0.142, P=0.039). However, the sera AQP-4antibody level was not correlated with the time to next attack and the conversion time of LETM to NMO(r=-0.29, P=0.073; r=-0.141, P=0.458).3. Among the78patients suffering form NMO, the seropositivity rate of sera AQP-4antibody was73.1%.4. By Spearman analysis, it was obvious that EDSS scores at acute stage, number of segments of spinal cord involved and brain MRI lesions were positively correlated to AQP-4antibody levels (r=0.423, P=0.0001; r=0.355, P=0.002; r=0.286, P=0.022). But the sera AQP-4antibody level did not correlate with the interval period to the next attack(r=0.126,P=0.532).Conclusions1. Among the78NMO patients and the49AQP-4Ab positive patients with first-ever LETM, the result proved that serum AQP4antibody levels positively correlated with EDSS scores at acute stage, else the number of segments of spinal cord involved. It indicated that the AQP-4antibody titres in acute phase can point the severity and the activity of disease and the AQP-4antibody may involve in the pathopoiesis in NMO.2. The EDSS scores at last visit, were also associated with the AQP-4antibody levels at first episode in sero-positive LETM. The positive correlation indicated that NMO-IgG antibodies were useful to predict the final disability.3. The number of brain lesions were positively associated with the titres of AQP-4antibody in NMO patients. It was possible that AQP-4antibody played an important role in the formation of brain lesions.4. In seropositive LETM, the interval period to the next attack and the conversion period of LETM to NMO were not related with AQP-4antibody levels. In NMO patients, the sera AQP-4antibody level in acute phase lacked the statistical correlation with the interval period to the next attack. It suggested that the single AQP-4antibody status may not have predictive value for the relapse and conversion.更多还原