血清水通道蛋白4抗体测定对视神经脊髓炎的诊断及预后判断价值

 目的:探讨血清水通道蛋白4（AQP4）抗体检测对视神经脊髓炎（NMO）诊断及预后判断的临床价值。 方法:  收集2010年1月至2013年12月在温州医科大学附属第一医院神经内科住院或门诊就诊的48例NMO、33例脊髓炎（TM）［包括26例长节段脊髓炎(LETM)和7例复发性脊髓炎(rLETM)］、30例视神经炎（ON） ［包括25例双眼视神经炎（BON）和5例复发性视神经炎（RION）］、52例多发性硬化（MS）及16例其它神经系统疾病（OND）的患者血清及相关临床资料。采用细胞免疫荧光法检测血清AQP4抗体。分析各组患者血清AQP4抗体的阳性率及抗体滴度,比较AQP4抗体阳性NMO患者与AQP4抗体阴性患者的临床特征。通过绘制受试者工作特征曲线（ROC曲线）,评价AQP4对NMO诊断的敏感性和特异性。应用Kaplan-Meier曲线分析血清AQP4抗体阳性患者进展为NMO的累计概率。 结果: NMO组AQP4抗体阳性率最高（87.50％）,其后依次为rLETM组（85.71%）、RION组（80.00%）、LETM组（30.70%）、 BON组（8.00%）和MS组（3.85%）, OND组抗体检测为阴性。NMO组中血清AQP4抗体阳性患者在性别构成比、确诊为NMO时间及伴有严重神经炎的比例等方面,与抗体阴性患者相比差异有统计学意义（P<0.05）。ROC曲线提示血清AQP4抗体对诊断NMO的敏感性为87.5%,特异性为85.4%。Kaplan-Meier曲线提示AQP4抗体阳性患者进展为NMO的累积概率明显高于抗体阴性的患者（P<0.05）。 结论: 血清AQP4抗体检测对诊断NMO具有较高的敏感性及特异性,且有助于NMO预后和转归的判断。     

特发性膜性肾病患者血清抗磷脂酶A2受体抗体与尿中IgG4检测的临床意义

目的：探讨特发性膜性肾病（IMN）患者血清抗磷脂酶A2受体（PLA2R）抗体及尿IgG4检测的临床意义。方法：将90例膜性肾病（MN）患者按照病理类型分为特发性膜性肾病（IMN）组（52例）和继发性膜性肾病（SMN）组（38例）;另选同期体检健康者35例作为对照组。检测各组血清抗PLA2R抗体表达和尿IgG4水平;分析治疗后不同转归的IMN患者之间的血清抗PLA2R抗体阳性率及尿IgG4水平差异。结果：IMN组的血清抗PLA2R抗体阳性率及尿IgG4水平均明显高于SMN组和对照组（P＜0.05）;SMN组的尿IgG4水平明显高于对照组（P＜0.05）,而血清抗PLA2R抗体阳性率与对照组差异无显著统计学意义（P＞0.05）;治疗后,IMN缓解组的血清抗PLA2R抗体阳性率明显低于未缓解组（P＜0.05）,治疗后尿IgG4水平较本组治疗前及未缓解组治疗后均降低（P＜0.05）,而治疗后未缓解组的尿IgG4水平较治疗前不降反升（P＜0.05）;IMN复发患者的血清抗PLA2R抗体阳性率及尿IgG4水平均明显高于无复发者（P＜0.05）。结论：IMN患者血清抗PLA2R抗体阳性率和尿IgG4水平明显升高,其变化与IMN的病情及远期结局均有关,二者联合检测有助于IMN的诊断、病情活动及预后评估。     

诱骗受体3γ-干扰素和抗环瓜氨酸肽抗体在风湿性关节炎患者血清中的表达

目的 分析在风湿性关节炎患者中抗环瓜氨酸肽抗体、血清诱骗受体3γ-干扰素检验有效性。方法 选择2018年1月~12月我院收治的风湿性关节炎患者50例作为观察组,另选同期体检健康人群40例作为对照组,检测并比较两组血清抗环瓜氨酸肽抗体、血清诱骗受体3γ-干扰素水平。结果 观察组抗环瓜氨酸肽抗体、风湿因子检测结果高于对照组,差异有统计学意义（P＜0.05）;观察组单一抗环瓜氨酸肽抗体检测阳性率、单一风湿因子检测阳性率均高于对照组,观察组抗环瓜氨酸肽抗体联合风湿因子检测阳性率高于对照组,差异均有统计学意义（P＜0.05）;观察组抗环瓜氨酸肽抗体、血清诱骗受体3γ-干扰素含量比对照组高,差异有统计学意义（P＜0.05）。结论 在风湿性关节炎患者中抗环瓜氨酸肽抗体、血清诱骗受体3γ-干扰素检验,能够明确患者临床指标情况,对于临床治疗有参考价值,值得应用。     

自身免疫性甲状腺病患者血清免疫球蛋白及甲状腺自身抗体、ANA、抗ENA抗体变化及临床意义

目的 探讨自身免疫性甲状腺病(AITD)患者血清免疫球蛋白及甲状腺自身抗体、抗核抗体(ANA)、抗可溶性抗原(ENA)抗体水平变化及临床意义.方法 选取2017年1月1日至2020年8月1日我院收治的110例AITD患者作为研究对象,包括桥本甲状腺炎(HT)和毒性弥漫性甲状腺肿(GD),其中HT组共62例,GD组共48例,另外选取同期60例健康体检者作为对照组,采集所有受检者静脉血,应用免疫学方法分别检测其血清免疫球蛋白以及甲状腺自身抗体、ANA、抗ENA抗体水平.结果 3组自身免疫球蛋白IgM、IgG和IgA水平比较差异均具有统计学意义(P＜0.05),其中HT组患者IgM和IgG水平显著高于对照组(P＜0.05),GD组患者IgG和IgA水平显著高于对照组(P＜0.05),且HT组IgM和IgG水平显著高于GD组,IgA水平显著高于GD组(P＜0.05);3组TPOAb和TGAb水平比较差异均具有统计学意义(P＜0.05),其中HT组明显高于GD组和对照组,GD组明显高于对照组(P＜0.05);在AITD患者中ANA和抗双链DNA (ds-DN A)抗体阳性率显著高于对照组(P＜0.05),抗U1-RNP抗体阳性率比较差异无统计学意义(P＞0.05);而在所有受检者中均未检出ENA谱中其他抗体.结论 血清免疫球蛋白和血清甲状腺自身抗体检测对AITD的临床鉴别诊断具有一定积极的指导意义;ANA与抗ENA抗体在AITD中并无特异性,关于其确切病理机制和意义有待进一步深入研究.     

系统性红斑狼疮患者血清抗dsDNA抗体的表达水平变化及临床意义分析

目的：通过检测系统性红斑狼疮（SLE）患者血清中抗dsDNA抗体,探讨抗dsDNA抗体在SLE的诊断与治疗中的临床意义。方法：用间接结合的放射性核素检测法（radioisotopic methods）检测SLE患者及疾病对照组（原发性干燥综合征,系统性硬化征,类风湿关节炎,多发性肌炎,混合性结缔组织病,强直性脊柱炎等）血清中的抗dsDNA抗体,同时评估SLE患者的各种临床表现（SLEADI）及实验室指标,并分析其与抗dsDNA抗体的相关性。结果：①60例SLE患者中有39例抗dsDNA抗体为阳性,阳性率为65%,抗dsDNA抗体,在33例对照组中有2例为阳性,阳性率为6.7%,抗dsDNA抗体在SLE的敏感性为65%,特异性为93.3%;②抗dsD-NA抗体与Sm抗体无相关性（P〉0.05）;与抗SSA抗体有相关性（P〈0.05）;③抗dsDNA抗体阳性患者的脱发,皮疹,口腔溃疡,蛋白尿等临床表现的发生率明显高于阴性患者（P〈0.05）;④抗dsDNA抗体阳性患者的白细胞、血小板降低等的发生率明显高于阴性患者,差异有绝对统计学意义（P〈0.05）。结论：抗dsDNA抗体作为SLE的特异性标记的抗体,其表达与疾病的活动性及严重程度密切相关。     

抗CCP抗体和RF联检在RA诊疗中的临床价值

目的：研究抗环瓜氨酸肽（anti-cyclic citrullinated peptide,Anti-CCP）（抗CCP抗体）和RF的检测在类风湿关节炎（RA）诊疗中的临床价值。方法：分别用酶联免疫吸附试验（ELISA）、BeckMan全自动蛋白分析仪同时检测早期RA组（病程〈1年）42例,RA组（病程〉1年）40例,非RA对照组40例患者血清抗CCP抗体和RF。结果：早期RA组、RA组的抗CCP抗体、RF阳性率显著高于非RA对照组（P〈0.05）RA组抗CCP水平显著高于早期RA组（P〈0.01）,两者RF无显著差别（P〉0.05）。RA组与早期RA组CCP抗体与RF二者无相关性。结论：联检抗CCP抗体、RF有助于类风湿的早期诊断和预测病情的进展。     

抗CCP抗体和抗MCV抗体在RA中的表达及意义

为探讨抗环瓜氨酸肽(cyclic citrullinated peptide, CCP)抗体和抗突变型瓜氨酸波形蛋白(mutated citrullinated vimentin, MCV)抗体在RA中的表达及临床意义,选择185例RA初诊患者作为RA组,70例其他风湿性疾病患者作为疾病对照组,80例健康者作为健康对照组,采用ELISA检测入选对象的血清抗CCP抗体、抗MCV抗体和RF水平,并监测其治疗前后的浓度变化情况。结果显示,抗CCP抗体和抗MCV抗体在RA组患者中的表达水平显著高于疾病对照组和健康对照组(P0.05);抗CCP抗体和抗MCV抗体诊断RA的灵敏度分别为83.8%和91.4%,诊断RF阴性RA的灵敏度分别为65.2%和81.0%。抗CCP抗体和抗MCV抗体在关节肿胀数 3、Sharp评分 50、DAS28高评分RA患者中的水平明显升高(P0.05),抗MCV抗体水平在CRP 50 mg/L、有关节腔积液的RA患者中明显升高(P0.05)。在RA缓解组中,抗MCV抗体水平在治疗3个月后明显下降(P0.05),抗CCP抗体在治疗6个月后明显下降(P0.05);在RA未缓解组中,抗CCP抗体和抗MCV抗体水平在治疗前后差异均无统计学意义(P 0.05)。提示抗CCP抗体和抗MCV抗体不仅在RA诊断和治疗中有较高的临床意义,两者联合检测还有利于对RA患者骨破坏情况、炎症反应等临床特征进行判断。     

不孕及反复自然流产患者血清抗精子抗体分析

目的：探讨不孕及反复自然流产与抗精子抗体（AsAb）的关系。方法：用金标法检测有反复自然流产史患者245例（流产组）、原发或继发不孕患者164例（不孕组）及正常妇女40例（对照组）血清中的AsAb。结果：不孕组AsAb总阳性率52.44%,流产组总阳性率48.57%,与对照组比较差异均有统计学意义（P〈0.05）。结论：AsAb与不孕及反复自然流产有着密切关系。     

复发性流产患者抗精子抗体检测与分析

目的探讨抗精子抗体在复发性流产患者孕前检查中的应用价值。方法选取420例有复发性流产史患者作为试验组,其中男189例,女231例,对其进行抗精子抗体检测;同时选取有正常生育史的45例男性与65例女性作为参照组,对两组的抗精子抗体的检测结果进行比较分析。结果试验组女性的阳性率为10.39%,男性的阳性率为7.26%,对照组女性的阳性率为1.54%,男性对照组中无人发现抗体阳性,RSA组的抗体阳性率明显高于正常对照组,差别有统计学意义（P〈0.05）。结论 As Ab的产生与RSA密切相关,在对复发性流产患者的优生咨询中,需重视免疫学因素。     

白癜风患者血清免疫球蛋白、补体、自身抗体检测及分析

目的 检测白癜风患者血清中免疫球蛋白IgG、IgA、IgM,补体C3、C4,抗核抗体(ANA)、抗甲状腺过氧化物酶抗体(A-TPO)、抗甲状腺球蛋白抗体(A-TG)的水平并进行比较分析.方法 收集门诊确诊为白癜风的患者血清168例和正常体检人群血清88例,性别、年龄分布无统计学差异,采用速率散射比浊法检测白免疫球蛋白IgG、IgA、IgM和补体C3、C4,采用ELISA法检测抗核抗体,采用电化学发光免疫分析法检测A-TPO、A-TG,结果用SPSS19.0统计软件进行分析.结果 白癜风患者组血清中免疫球蛋白IgG、IgA、IgM,补体C3、C4表达水平与正常人对照组差异不具有统计学意义(P＞0.05);白癜风组与正常对照组ANA阳性率分别为8.1％和5.7％,经比较差异不具有统计学意义(P＞0.05);两组间A-TPO的阳性率分别为18.8％和10.2％,差异有统计学意义(P＜0.05);两组A-TG阳性率分别为25.8％和4.5％,经比较差异具有统计学意义(P＜0.01).结论 部分白癜风患者存在体液免疫紊乱,在发病机制上可能与自身免疫性甲状腺疾病有相似之处;免疫球蛋白、补体及抗核抗体等免疫指标的检测在白癜风诊治中评价的意义不大.     

Treatment of neuromyelitis optica

Neuromyelitis optica (NMO) or Devic's disease is an inflammatory neurologic disease characterized by severe optic neuritis and transverse myelitis. Other features of NMO include female preponderance, higher onset age, severe functional disability, longitudinally extensive spinal cord lesions (longer than 3 vertebral segments), and oligoclonal IgG bands negativity. Brain lesions are not uncommon in NMO. The relation between NMO and multiple sclerosis (MS) has long been a matter of controversy, but since the discovery of anti-aquaporin 4 (AQP4) antibody (NMO-IgG), an NMO-specific autoantibody, the clinical, MRI, and laboratory features that distinguish NMO from MS have been clarified. Anti-AQP4 antibody binds to the extracellular domain of AQP4, which is highly expressed in endfeet of astrocytes. Recent neuropathological studies, analysis of CSF-GFAP levels during relapse and experimental studies strongly suggest that NMO is an anti-AQP4 antibody-mediated astrocytopathic disease and that T cell-mediated CNS inflammation is necessary to develop NMO. Also, IL-6 is remarkably elevated in the CSF and appears to regulate plasmablasts to produce anti-AQP4 antibody. Therefore, from the therapeutic point of view, depletion of anti-AQP4 antibody, suppression of T cell response to trigger relapse and anti-IL-6 therapy seem to be pivotal. High-dose intravenous methylprednisolone is the first-line therapy for acute exacerbations of NMO. But plasma exchange should be started soon if corticosteroid is not efficacious. If untreated, AQP4 antibody-positive patients are highly likely to experience relapses within a year. Thus, immunosuppressive therapy (corticosteroids, immunosuppressants, rituximab) should be initiated without delay. Preliminary results suggest that eculizumab, an anti-C5 monoclonal antibody, can also prevent relapse in NMO, Meanwhile, interferon-beta, a first-line disease modifying drug of MS, is not effective in NMO. Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life.     

模拟抗原ELISA检测视神经脊髓炎患者血清水通道蛋白-4抗体

目的 初步探讨以人工合成多肽模拟抗原酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测视神经脊髓炎(neuromyelitis optica,NMO)患者血清水通道蛋白-4(aquaporin-4,AQP4)抗体.方法根据AQP4蛋白的分子构成和三级结构,应用生物信息学和结构生物学的方法设计3段AQP4蛋白膜外段多肽片段,分别为AQP456-69、AQP4135-155、AQP4209-230;以其为抗原ELISA检测9例NMO及神经科其他疾病7例患者血清,并与免疫荧光法检测结果进行对比分析.结果 以AQP4135-155、AQP4209-230为抗原ELISA检测结果显示,9例NMO患者中,7例经免疫荧光法证实AQP4抗体阳性患者吸光度A值平均值比阴性对照患者显著提高(P＜0.05);当血清稀释4倍和8倍时具有较高的A值,与对照组相比差异具有统计学意义(P＜0.05).结论 AQP4蛋白2段膜外段多肽,即AQP4135-155和AQP4209-230可能是NMO患者血清中AQP4抗体所针对的主要抗原表位或抗原表位的主要部分,初步表明模拟抗原ELISA检测NMO患者血清AQP4抗体的可行性.     

Reappraisal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients

Selective aquaporin‐4 (AQP4) loss and vasculocentric complement and immunoglobulin deposition are characteristic of neuromyelitis optica (NMO). We recently reported extensive AQP4 loss in demyelinated and myelinated layers of Baló's lesions without perivascular immunoglobulin and complement deposition. We aimed to reappraise AQP4 expression patterns in NMO and multiple sclerosis (MS). We evaluated AQP4 expression relative to glial fibrillary acidic protein, extent of demyelination, lesion staging (CD68 staining for macrophages), and perivascular deposition of complement and immunoglobulin in 11 cases with NMO and NMO spectrum disorders (NMOSD), five with MS and 30 with other neurological diseases. The lesions were classified as actively demyelinating (n = 66), chronic active (n = 86), chronic inactive (n = 48) and unclassified (n = 12). Six NMO/NMOSD and two MS cases showed preferential AQP4 loss beyond the demyelinated areas, irrespective of lesion staging. Five NMO and three MS cases showed AQP4 preservation even in actively demyelinating lesions, despite grave tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO/NMOSD patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Our present and previous findings suggest that antibody‐independent AQP4 loss can occur in heterogeneous demyelinating conditions, including NMO, Baló's disease and MS.     

Neuromyelitis optica and opticospinal multiple sclerosis: Mechanisms and pathogenesis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. In Asians, MS is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal MS (OSMS), has similar features to the relapsing form of NMO in Western populations. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin-4 (AQP4), one of the major water channel proteins in the CNS. Because NMO-IgG has been reported to be present in 30-60% of OSMS patients, OSMS in Asians has been suggested to be the same entity as NMO.The sensitivity of NMO-IgG/anti-AQP4 antibody for NMO varies from 30% to 80%, while the specificity is 90-100%. Pathological studies on NMO have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, where myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complements, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. It is thus postulated that the complement-activating anti-AQP4 antibody plays a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event.However, in autopsied cases of NMO, we and others found that some demonstrated selective AQP4 loss while others showed preservation of AQP4, even in the acute lesions. We also found that, in some MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. In the CSF, proinflammatory cytokines such as IL-17, IL-8, IFNγ, and G-CSF are markedly elevated in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. In OSMS and NMO patients, T cells reactive to myelin proteins show intra- and inter-molecular epitope spreading, suggesting that T cells are already stimulated with myelin antigens in vivo. These findings suggest that mechanism of NMO and OSMS in Asians is heterogeneous, anti-AQP4 antibody-related and -unrelated, and that not only anti-AQP4 antibody but also myelin-autoreactive Th17 or Th1 cells may also play a role in triggering CNS inflammation. Possible mechanisms for NMO and OSMS are discussed in this review.     

Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature

Antibodies to aquaporin‐4 (called NMO‐IgG or AQP4‐Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO‐IgG/AQP4‐Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO‐IgG/AQP4‐Ab testing. All available immunoassays—including tissue‐based (IHC), cell‐based (ICC, FACS) and protein‐based (RIPA, FIPA, ELISA, Western blotting) assays—and their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO‐IgG/AQP4‐Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO‐IgG/AQP4‐Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4‐M1 vs. AQP4‐M23‐based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO‐IgG/AQP4‐Ab serology are given.     

Association of the HLA-DPB1*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders

There are two subtypes of multiple sclerosis (MS) in Asians: the opticospinal (OSMS) form that shows a selective involvement of the optic nerve and the spinal cord and the conventional (CMS) form that has disseminated lesions in the central nervous system including the cerebrum, cerebellum and brainstem. Both show distinct human leukocyte antigen (HLA) class II associations. OSMS has similar features to the relapsing form of neuromyelitis optica (NMO) in Western populations. Recently, it was shown that antibodies to aquaporin-4 (AQP4) are specifically detected in NMO patients and in some Japanese patients with OSMS or recurrent optic neuritis or myelitis. To clarify the immunogenetic background of anti-AQP4 antibody production, we studied HLA-DRB1 and -DPB1 gene polymorphisms in anti-AQP4 antibody-positive and -negative patients with idiopathic demyelinating diseases, such as MS, recurrent optic neuritis and recurrent myelitis. The phenotypic frequency of the HLA-DPB1*0501 allele was significantly increased in anti-AQP4 antibody-positive patients (89.5%, odds ratio = 4.8; 95% confidence interval = 1.6–14.3, n  = 38, P^corr  = 0.032) compared with controls (64.0%, n  = 125) but not in either anti-AQP4 antibody-negative OSMS (75.0%, n  = 32) or CMS (69.2%, n  = 52) patients. There was no significant correlation between any HLA-DRB1 allele and the existence of anti-AQP4 antibody. These findings suggest that the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB1*0501 allele in Japanese.     

Early and extensive spinal white matter involvement in neuromyelitis optica

ObjectivesStudies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin‐4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO.MethodsWe analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3‐tesla MRI in 15 AQP4 antibody‐positive NMO/NMOSD patients and in 15 AQP4 antibody‐negative multiple sclerosis (MS) patients.ResultsPathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty‐four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, P ^corr = 0.020, and P ^corr = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti‐AQP4 antibody‐seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, P ^corr = 0.005, and P ^corr = 0.043, respectively) and AQP4 antibody‐seronegative MS patients (86.7%, 73.3% and 33.3%, P ^corr = 0.063, and P ^corr = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively.ConclusionsNMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.     

细胞免疫荧光法在视神经脊髓炎患者血清及脑脊液中水通道蛋白4抗体检测中的运用价值

目的 探讨细胞免疫荧光法(CBA)在视神经脊髓炎患者血清与脑脊液水通道蛋白4抗体(AQP4-Ab)检测中的运用价值.方法 选择多发性硬化患者52例为硬化组,视神经脊髓炎患者54例为脊髓炎组,体检正常的自愿者50例为正常组.分别采用组织间接免疫荧光检测(IIF)、细胞免疫荧光法(CBA)和酶联免疫吸附法(ELISA)检测血清和脑脊液标本(正常组未提取)的AQP4-Ab,比较各方法AQP4-Ab的阳性检出率、特异性和灵敏度.结果 CBA、IIF和ELISA对脊髓炎组血清标本和脑脊液标本的AQP4-Ab阳性检出率显著高于硬化组和正常组(P<0.05).CBA对脊髓炎组患者脑脊液标本和血清标本的AQP4-Ab阳性检出率分别为87.04%、70.37%,显著高于其他两种方法(P<0.05).不同方法对脊髓炎组患者血清和脑脊液标本AQP4-Ab检测的敏感性为:CBA>IIF>ELISA,且有统计学差异(χ2=7.394、14.687,P<0.05),但是不同方法的特异性无差异(P>0.05).结论 AQP4-Ab阳性表达与视神经脊髓炎的发生有一定关系.在CBA、IIF和ELISA等检测方法中,CBA的阳性检出率和灵敏度最高,适宜视神经脊髓炎的早期诊断.     

Clinical Spectrum and Treatment of Neuromyelitis Optica Spectrum Disorders: Evolution and Current Status

Neuromyelitis optica (NMO) is an inflammatory neurologic disease clinically characterized by severe optic neuritis (ON) and transverse myelitis (TM). The relationship between NMO and multiple sclerosis (MS) has long been a matter of debate. However, the discovery of an NMO‐specific autoantibody, NMO‐immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our understanding of the disease, and the clinical, magnetic resonance imaging (MRI), optical coherence tomography, and laboratory examinations have clarified unique features of NMO that are distinct from MS. The term NMO spectrum disorders (NMOSD) incorporating spatially limited forms was introduced, as patients with recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM (LETM) alone are also often AQP4 antibody‐seropositive. Moreover, studies of seropositive cases have shown that more than half of them have brain lesions, some of which are unique to NMO, and can be the onset manifestation. Some clinical features of AQP4 antibody‐seronegative NMO differ from seropositive, but it remains unknown whether they are pathologically distinct. Immunosuppressive treatments are effective for acute attacks and prevention of relapses of NMOSD, and new molecularly targeted drugs are under investigation. Importantly, some disease modifying drugs for MS may exacerbate NMOSD, making early differential diagnosis of the two diseases crucial. We review the evolving clinical spectrum, the updated clinical, MRI, neuro‐ophthalmological and laboratory findings, and the current status of treatment in NMOSD.