多发性硬化脑脊液寡克隆区带及24小时鞘内IgG合成率检测的比较

采取垂直平板聚丙烯酰胺凝胶电泳法、火箭免疫电泳法对30例多发性硬化病人进行脑脊液寡克隆区带及24小时鞘内IgG合成率的检测,结果发现寡克隆区带、合成率与多发性硬化的发病年龄、病程、病程进展类型、病残程度无统计学上的相关性,寡克隆区带阳性率46.7％,合成率增高占60％,两者合计异常率可达73.3％,提示我国多发性硬化寡克隆区带阳性率、合成率增高均较国外低,因而在我国对多发性硬化的实验室诊断两者同时检测更有意义。     

抗N-甲基-D-天冬氨酸受体脑炎患者的脑脊液指标异常及其与病程相关性分析

目的分析抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者脑脊液常规、生化及免疫参数特征,探讨脑脊液指标在诊断及指导治疗该病中的价值。方法收集63例确诊为抗NMDAR脑炎患者的临床资料。检测脑脊液常规、生化及IgG指数、24 h鞘内IgG合成率、寡克隆区带和血脑屏障破坏情况,并对脑脊液指标和临床表现进行分析。结果 63例抗NMDAR脑炎患者脑脊液白细胞计数、蛋白含量增高的比例分别为49.2%和30.2%;24 h鞘内IgG合成率增高、IgG指数增高、寡克隆区带阳性和血脑屏障破坏的比例分别为33.3%、28.6%、28.6%和34.9%。38例(60.3%)脑脊液白细胞升高或寡克隆区带阳性。抗NMDAR脑炎发病1个月脑脊液异常仅为白细胞升高而无寡克隆区带阳性患者的比例显著高于发病1个月者(P0.05);而发病1个月鞘内IgG合成异常患者的比例率显著低于发病1个月患者(P0.05)。脑脊液白细胞计数与检测时的病程时间呈负相关(r=-0.284,P0.05),而脑脊液蛋白水平与检测时的病程时间呈正相关(r=0.308,P0.05)。结论抗NMDAR脑炎存在中枢神经系统的炎症反应,但中国人群中抗NMDAR脑炎患者出现脑脊液异常的比例不高。病程早期脑脊液异常表现以白细胞增多为主,病程中后期以鞘内IgG合成增加、出现寡克隆区带为主,提示抗NMDAR脑炎在不同临床阶段具有不同的脑脊液异常表现。     

多发性硬化患者IgG指数、24 h合成率、组分区带检测的比较

目的 研究IgG指数，24h合成率，组分区带对多发性硬化（MS）患者的临床意义。方法 应用免疫比浊法，等电点聚焦及银染色法进行检测。结果 103例经临床诊断为MS患者中IgG组分区带阳性占90.3%，IgG24h合成率异常占19.4%,IgG指数异常占17.5%。结论 MS患者IgG组分区带阳性率比IgG指数，IgG24h合成率高，对MS有辅助性诊断意义。     

寡克隆区带和IgG指数对多发性硬化的诊断价值

目的　探讨寡克隆区带 (OCB)和IgG指数对多发性硬化 (MS)诊断的敏感性及特异性。方法　收集 4 8例MS、6 8例神经系统炎性疾病 (NID)及 110例非炎性疾病 (NNID) 3组患者的脑脊液 (CSF)和血清标本 ,分别进行OCB的检测 (等电聚焦 )和IgG指数的计算。并对其阳性结果似然比 (PRLR)进行分析。结果　MS组与NID组比较 ,CSF中OCB阳性率和IgG指数异常率的差异均没有显著性 (均P >0 0 5 ) ;但MS组、NID组与NNID组比较 ,差异均有极显著性 (均P <0 0 0 0 1)。MS组CSF中OCB和IgG指数的敏感性分别为 39 6 %、6 0 4 % ;特异性分别为 80 3%、72 1% ;PRLR分别为 2 0、2 2。当用于判断有无IgG鞘内合成时 ,特异性分别为 97 2 %、92 7% ;PRLR分别为 13 5、7 3。结论　CSF中OCB阳性和IgG指数升高强烈提示有中枢神经系统局部IgG合成 ,对MS有一定的辅助诊断价值     

神经梅毒合并猫立克次体感染一例并文献复习

目的 报道1例神经梅毒合并猫立克次体感染患者,并总结其临床表现、脑脊液检查和影像学特点。方法与结果 首都医科大学附属北京天坛医院于2022年10月12日收治1例33岁男性患者,病程3月余,家中养猫10余年。临床主要表现为癫痫发作、认知功能下降,近1个月出现低热。血清梅毒螺旋体抗体阳性,梅毒螺旋体血凝试验阳性,甲苯胺红不加热血清试验阳性;脑脊液白细胞计数增加,蛋白定量升高,寡克隆区带阳性,24小时鞘内IgG合成率和IgG指数升高。头部MRI显示双侧颞叶内侧T2WI和FLAIR成像高信号,海马萎缩,以右侧显著。脑脊液宏基因组第二代测序技术（mNGS）检出猫立克次体序列数为229条、梅毒螺旋体序列数为2条。追问病史,患者7年前曾患有梅毒,复查血清和脑脊液梅毒螺旋体抗体均呈阳性。综合患者临床和影像学表现,符合神经梅毒特点,发热符合猫立克次体感染特点,临床明确诊断为神经梅毒合并猫立克次体感染,予以青霉素和多西环素治疗后改善。结论神经梅毒合并猫立克次体感染临床罕见,mNGS有助于早期诊断,尽早抗感染治疗,可以有效改善患者预后。     

脑脊液TRUST及TPPA检测对于神经梅毒的诊断价值

目的 研究两种神经梅毒检测方法 [梅毒甲苯胺红不加热血清试验(TRUST)和梅毒螺旋体明胶凝集试验(TPPA)]的特异性、敏感性和关联性,进一步探讨两者对神经梅毒诊断和判断疗效的价值. 方法 采用TRUST和TPPA检测255例HIV阴性患者的血液和脑脊液标本,对确诊为神经梅毒的患者运用大剂量青霉素治疗,半年后复查血液和脑脊液TRUST和TPPA.比较两种检测方法 的敏感性、特异性、关联性以及半年后两种检测方法 的转阴率. 结果 255例患者中有103例确诊为神经梅毒.脑脊液TRUST检测神经梅毒的敏感性和特异性分别为78.64%、99.34%,脑脊液TPPA检测神经梅毒的敏感性和特异性均为100%,两种检测方法 检出阳性率比较差异有统计学意义(P＜0.05).治疗半年后92例患者复查血液TRUST和血液TPPA,76例患者复查脑脊液TRUST和脑脊液TPP,发现脑脊液TRUST、脑脊液TPPA、血液TRUST、血液TPPA的转阴率分别为25%(15/60)、0(0/76)、1.87%(1/92)、0(0/92),脑脊液TRUST转阴率较血液TRUST转阴率高,比较差异有统计学意义(P＜0.05). 结论 脑脊液TPPA应作为神经梅毒的确诊病例标准,脑脊液TRUST可作为其疗效参考指标.     

脑脊液寡克隆区带对多发性硬化的意义

目的探讨脑脊液寡克隆区带(oligoclonal bands,OCB)在多发性硬化(multiple sclerosis,MS)中的意义。方法收集神经系统疾病患者895例,其中MS患者151例,视神经脊髓炎(neuromyelitis optica,NMO)患者92例,其他神经系统脱髓鞘疾病(other demyelinating diseases,ODD)患者122例,其他神经系统炎性疾病(other inflammatory neurological diseases,IND)患者99例,神经系统非炎性疾病(noninflammatory neurologicaldiseases group,NIND)患者431例。检测所有患者的OCB、IgG指数及24hIgG合成率,比较各组OCB阳性、IgG指数及24hIgG合成率升高情况,并比较OCB阳性和阴性MS患者的主要临床特点。结果 OCB阳性率MS组为32.45%,NMO组为20.65%,ODD组为18.03%,IND组为16.16%,NIND组为2.09%;IgG指数升高比例MS组为29.8%,NMO组为17.39%,ODD组为16.39%,IND组为15.15%,NIND组为1.62%;24hIgG合成率升高比例MS组为30.46%,NMO组为18.48%,ODD组为18.85%,IND组为19.19%,NIND组为1.39%。OCB阳性率、IgG指数和24hIgG合成率升高比例MS组均高于其他各组(均P<0.05);NMO组与ODD组、IND组的OCB阳性率、IgG指数和24hIgG合成率升高比例无统计学差异(均P>0.05);MS组、NMO组、ODD组及IND组OCB阳性率均高于NIND组(均P=0.000)。OCB阳性MS患者的女性比例、EDSS评分、IgG指数和24hIgG合成率〔分别为女∶男2.5∶1、(4.10±1.49)、(0.81±0.31)、(4.98±3.35)〕均高于OCB阴性患者〔分别为女∶男1.17∶1、(3.47±1.39)、(0.51±0.17)、(3.37±3.20)〕(均P<0.05)。结论与其他中枢神经系统疾病相比,MS患者的OCB阳性率更高。OCB阳性MS患者的女性比例、EDSS评分、IgG指数和24hIgG合成率均高于OCB阴性患者。     

寡克隆区带和IgG指数在多发性硬化中的诊断意义

目的研究寡克隆区带（OCBs）和IgG指数（IgGI）对多发性硬化（MS）诊断的敏感性及其影响因素。方法用等电聚焦结合银染色法检测30例MS、40例神经系统炎性疾病（NID）和22例神经系统非炎性疾病（NNID）患者CSF中OCBs，并计算IgG I。结果MS组和NID组比较OCBs阳性率、IgG I异常率均无显著性差异（P〉0．05）；MS组、NID组与NNID组比较。差异均有显著性（P〈0．05）；传统型MS和脊髓型MS比较，差异均无显著性（P〉0．05）。OCBs对MS诊断的敏感性、特异性和阳性结果似然比分别为63．3％、77．7％和2．8；IgG I分别为40．0％、76．7％和1．7。结论本地区MSOCBs阳性率和IgG I异常率较低，可能与遗传背景、疾病类型和药物应用有关，OCBs和IgG I对MS诊断具有相对特异性。     

多发性硬化患者脑脊液血清配对标本蛋白质系列指标的分析

目的　分析蛋白系列指标,判断血脑屏障通透性,明确 Ｉｇ Ｇ 来源。方法　用考马斯亮蓝 Ｇ２５０ 法测定总蛋白,聚丙烯酰胺凝胶电泳银染色法测定寡克隆区带,火箭免疫电泳法同时测定 Ｉｇ Ｇ 和白蛋白, Ｃ Ｓ Ｆ Ａｌｂ／ Ｓｅｒｕｍ Ａｌｂ 比值判断血脑屏障通透性。结果　３０ 例多发性硬化患者 ２２ 例血脑屏障通透性正常,其蛋白系列指标阳性率： Ｏ Ｃ Ｂ 为 ５４．５％ , Ｉｇ Ｇ 合成率为 ６３．６％ , Ｃ Ｓ Ｆ Ｉｇ Ｇ／ Ｃ Ｓ Ｆ Ａｌｂ 比值为 ４０．９％ , Ｃ Ｓ Ｆ Ｉｇ Ｇ／ Ｃ Ｓ Ｆ Ｔ Ｐ 为 ４５．５％ , Ｃ Ｓ Ｆ Ｉｇ Ｇ 为 ４５．５％ , Ｏ Ｃ Ｂ＋ Ｉｇ Ｇ 合成率为 ８１．８％ 。结论　在判断清楚血脑屏障通透性是正常还是异常的前提下再分析蛋白系列指标,并且以寡克隆区带和 Ｉｇ Ｇ 合成率为主要指标,只有血脑屏障通透性正常而寡克隆区带和 Ｉｇ Ｇ 合成率又异常时,才能肯定的认为有中枢鞘内 Ｉｇ Ｇ（抗体）的合成。     

寡克隆带和IgG鞘内合成率对多发性硬化的诊断价值

目的探讨寡克隆带(OCBs)和IgG鞘内合成率(IgGSyn)对多发性硬化(MS)诊断的敏感性、特异性,以及定性和定量指标的相关性。方法选取30例MS(MS组)、40例神经系统炎性疾病(NID组)和22例神经系统非炎性疾病(NNID组)患者,应用速率散射比浊法测定血清和脑脊液(CSF)中免疫球蛋白G(IgG)、白蛋白(Alb)水平,等电聚焦结合银染色法检测CSF中OCBs,计算IgGSyn,并对其敏感性、特异性和阳性结果似然比(PRLR)进行分析。结果OCBs阳性率和IgGSyn异常率MS组与NID组比较差异无显著性;MS组、NID组与NNID组比较差异有极显著性(均P<0.01)。MS组和NID组中,OCBs阳性者与阴性者IgGSyn值差异无显著性。对MS诊断的敏感性、特异性和PRLR,OCBs分别为63.3%、77.7%和2.8;IgGSyn为46.7%、75.2%和1.9。结论OCBs和IgGSyn检测结果的不完全一致性提示中枢神经系统内存在不同的体液免疫反应机制,综合分析OCBs和IgGSyn,对MS诊断具有参考价值。     

Azathioprine reduces intrathecal IgG synthesis in multiple sclerosis

Intrathecal IgG synthesis and CSF oligoclonal bands were reexamined after 18-24 months in 66 patients with multiple sclerosis; 40 of them received azathioprine (AZA) 2.5 mg/Kg/die; all received a course of dexamethasone (DEXA) during clinical relapses. The IgG Index was significantly reduced in the group treated with AZA, especially in patients with short disease duration, low disability and high IgG index. Changes observed in CSF banding pattern were not significant. These results suggest an effect of AZA on IgG synthesis, as reported by in vitro studies.     

Herpes simplex virus encephalitis: Intrathecal synthesis of oligoclonal virus-specific IgG,IgA and IgM antibodies

Summary Paired specimens of serum and CSF from seven patients with acute herpes simplex virus encephalitis were examined during the acute illness or the convalescent stage or during both stages. Imprint immunofixation analyses of viral antibodies separated by agarose electrophoresis and by electrofocusing disclosed intrathecal production of herpes simplex virus IgG antibodies in all seven patients, and of IgA and IgM antibodies in six and three of six patients, respectively. Intrathecal production of herpes simplex virus-specific IgG and IgA was observed in two patients from whom samples were collected after 1 year, while intrathecal production of virus-specific IgM was not demonstrated later than 5 weeks after onset. The intrathecally synthesized IgG and IgM, and to a lesser extent IgA antibodies displayed oligoclonal characteristics. Oligoclonal bands of IgG were observed in the CSF of all patients. Evidence is presented to show that the bulk of the oligoclonal CSF IgG represents herpes simplex virus-specific antibodies. Intrathecally synthesized populations of herpes simplex virus antibodies cross-reacting with varicella-zoster virus were identified in three of the patients.     

GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence

Background and purpose:  Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS).
Methods:  To chart the avidity and clonal patterns of GAD65 IgG, we performed scatchard plot of binding characteristics and isoelectric focusing-immunoblot of cerebrospinal fluid (CSF) and serum from five SPS patients.
Results:  Oligoclonal GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in CSF and serum in all patients. The distribution of GAD65-specific IgG bands in serum and CSF revealed intrathecal synthesis of oligoclonal GAD65 IgG in all five patients, whilst radioimmunoassay demonstrated intrathecal synthesis of GAD65 IgG in four. The binding avidity of GAD65 IgG from CSF was more than 10 times higher than in serum in two of the patients but did not differ substantially in the remaining three. These differences were not related to symptom severity. The pattern of oligoclonal GAD65 IgG bands in CSF and serum in three patients examined remained unchanged for up to 7 years after symptom debut.
Conclusion:  This study confirms the persistent systemic and intrathecal production of GAD65-specific IgG in SPS, and further shows that this immune response is oligoclonal and mediated by a stable population of affinity maturated B cell clones.     

Cerebrospinal fluid free kappa light chains versus IgG findings in neurological disorders: qualitative and quantitative measurements

In this study free kappa light chains in cerebrospinal fluid (CSF) were determined both by an affinity mediated capillary blotting technique after isoelectric focusing (IEF) in agarose gel and by a quantitative enzyme linked immunosorbent assay (ELISA). The free kappa results were compared with the IgG findings in 4 neurological patient groups with a distinct CSF IgG pattern: (1) CSF without oligoclonal IgG bands, (2) CSF with serum derived IgG bands, (3) CSF restricted IgG bands and (4) CSF restricted and serum derived IgG bands. Oligoclonal free kappa bands are nearly absent in CSF of groups 1 + 2, and present in 88% of group 3 and 84% of group 4 patients. We could also establish free kappa indices from specimens in the 4 groups in analogy to IgG indices. Group 1 had a median free kappa index of 1.1, group 2: 1.0 and groups 3 + 4: 10.0. The correspondence between immunoblot and index findings for free kappa is better than for IgG. Free kappa index is more sensitive but somewhat less specific than IgG index for establishing intrathecal immune production.     

Intrathecal IgA synthesis in neurosyphilis

Neurosyphilis can develop during any stage of syphilis. It has recently been reported that cerebrospinal fluid (CSF) data from patients with parenchymal or meningovascular neurosyphilis all show the absence of IgA synthesis and occasionally a concomitant IgM synthesis. In this context, it has been stated that intrathecal IgA synthesis contradicts the diagnosis of neurosyphilis. In our CSF analysis of four patients with definite neurosyphilis we observed an intrathecal synthesis of IgA, IgG and IgM in two patients. Our data are consistent with data of other studies suggesting that about 50% of patients with neurosyphilis show intrathecal synthesis of IgA. Therefore, intrathecal synthesis of IgA does not necessarily contradict the diagnosis of neurosyphilis. We hypothesize that intrathecal synthesis of IgA does not necessarily serve as a discriminating feature between neurosyphilis and other inflammatory central nervous system (CNS) disorders and that other laboratory parameters and the clinical picture have to be taken into account as well.     

Qualitative evidence of anti-Yo-specific intrathecal antibody synthesis in patients with paraneoplastic cerebellar degeneration

We investigated the presence of anti-Yo-specific oligoclonal antibody bands in cerebrospinal fluid (CSF) and serum samples of 9 patients with anti-Yo syndrome and 11 controls. Isoelectric focusing combined with affinity blotting, revealed anti-Yo-specific intrathecal antibody synthesis in all patients with anti-Yo syndrome: Four patients had positive anti-Yo-specific oligoclonal IgG bands in CSF which were not demonstrable in their sera; five CSF/serum pairs showed additional, more intensive, oligoclonal bands in CSF compared to the corresponding serum. Interestingly, four patients with absence of oligoclonal bands of total IgG in CSF revealed positive anti-Yo-specific oligoclonal bands in the same sample. This speaks for a higher sensitivity of detection of oligoclonal bands using an affinity blot loaded with Yo-specific antigen compared to an affinity blot coated with anti-human IgG used for the detection of oligoclonal bands of total IgG. In conclusion, the presence of anti-Yo-specific oligoclonal IgG bands in CSF which were absent, or less strong, in patients sera provides qualitative evidence of anti-Yo-specific IgG synthesis by intrathecal B-cell clones. These results could be of interest in detection of intrathecal-specific IgG synthesis in nervous system infectious diseases provided that the target antigen is known.     

Blood-cerebrospinal fluid barrier permeability to serum IgG subfractions and measurement of intrathecal IgG synthesis

CSF/serum gradients of IgG subfractions separated by isoelectric focusing (IF) have been measured by high resolving laser densitometry. In patients with normal blood-CSF barrier permeability (N.25) and with barrier damage due to acute idiopathic polyneuropathy (N.15) and to medullary compression (N.17), the CSF/serum gradients of IgG subfractions were negatively correlated with their pI. This electrostatic selectivity appeared to be reverted in barrier damage due to acute meningoencephalitis (N.15). In a series of multiple sclerosis patients (N.31), the CSF/serum gradients of IgG subfractions lacking CSF oligoclonal bands have been used to assess the overall barrier permeability to serum IgG. All intra-BCB synthesized IgG subfractions could be measured by densitometry, whereas with other quantitative formulae, 23-26% of the results were false negatives; the total intrathecal IgG amount ranged from 0.01 to 11 mg/dl. The most frequent and prominent fractions appeared to be cathodic. Electrostatic and steric barrier selectivity must be taken into account when the amount of intrathecal IgG synthesis has to be measured.     

Immunoglobulin abnormalities in the cerebrospinal fluid during bacterial meningitis

11 patients with bacterial meningitis, examined during the course of the disease for immunoglobulin (Ig) abnormalities in the cerebrospinal fluid (CSF), all had an increased CSF IgM index equal to (CSF/serum IgM):(CSF/serum albumin), indicating intrathecal IgM production. Seven patients had a slightly increased CSF IgG index, and 7 a slightly increased IgA index. Six of the 11 patients had an increased IgM index in the presence of normal indices for IgG and IgA. Follow-up revealed the return of these values to normal. Four patients had identical oligoclonal IgG bands in the CSF and serum, probably representing a systemic immune response, but in only one case were oligoclonal bands suggestive of intrathecal IgG production found. No oligoclonal IgA response was demonstrable in the 4 patients examined. Antigen-immunofixation or antigen-absorption studies revealed evidence of a specific, intrathecal IgG antibody response in only 2 patients, while a search for IgG antibodies against aetiologically unrelated bacterial and viral antigens was negative. With the exception of IgM production, therefore, a humoral intrathecal immune response is less common in bacterial than in aseptic meningitis.