急性期多发性硬化患者脑脊液及血清髓鞘少突胶质细胞糖蛋白抗体、髓鞘相关生长抑制因子抗体的检测及其意义

目的 探讨急性期多发性硬化(MS)患者脐脊液(CSF)和血清髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)、髓鞘相关生长抑制因子抗体(Nogo-A-Ab)的异常率及其临床意义.方法 选取临床确诊的MS(急性发作期)患者30例、其他炎症性神经疾病(OIND)患者30例和非炎症性神经疾病(NIND)患者30例;应用ELISA法检测3组患者CSF、血清MOG-Ab及Nogo-A-Ab.结果 MS组CSF和血清MOG-Ab阳性率(46.7%,40.0%)与OIND组(10.0%,6.7%)及NIND组(3.3%,0)比较,差异有统计学意义(均P<0.05);OIND组与NIND组比较,差异无统计学意义;MS组CSF Nogo-A-Ab阳性率(36.7%)与OIND组(6.7%)及NIND组(0)比较,差异有统计学意义(均P<0.05),血清Nogo-A-Ab阳性率(10.0%)与OIND组(3.3%)及NIND组(0)比较.差异无统计学意义;OIND组CSF和血清Nogo-A-Ab阳性率与NIND组比较,差异均无统计学意义;MS组CSF与血清MOG-Ab阳性率比较,差异无统计学意义,CSF与血清Nogo-A-Ab阳性率比较,差异有统计学意义(P<0.05);MS组CSF MOG-Ab及Nogo-A-Ab同为阳性有7例(23.3%),而未见血清两者均阳性者.结论 MS患者急性期检测CSF及血清MOG-Ab,以及CSF Nogo-A-Ab有助于明确MS诊断.     

MOG抗体阳性视神经脊髓炎谱系疾病临床和影像学特点

目的探讨血清髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoprotein, MOG)抗体阳性的视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder, NMOSD)患者的临床和影像学特点。方法收集NMOSD患者57例、多发性硬化(multiple sclerosis, MS)患者29例,回顾性分析MOG抗体阳性的NMOSD患者的临床和影像学特点。结果 9/57(15.8%)NMOSD患者血清MOG抗体阳性,其中1例患者血清MOG与水通道蛋白-4(aquaporin-4, AQP4)抗体双阳性,2/29(6.9%)MS患者血清MOG抗体阳性,两组患者MOG抗体阳性率差异无统计学意义(P0.05)。MOG抗体阳性NMOSD患者男女比例为1:7,平均起病年龄为(41.4±11.5)岁,与MOG抗体阴性组以及AQP4抗体阳性组相比差异无统计学意义(P0.05)。MOG抗体阳性NMOSD组、MOG抗体阴性NMOSD组的病程均比AQP4抗体阳性NMOSD组短,差异有统计学意义(P均0.05),但MOG抗体阳性NMOSD组与MOG抗体阴性NMOSD组比较差异无统计学意义(P0.05)。三组患者均以复发为主,平均复发次数比较差异无统计学意义(P0.05)。MOG抗体阳性NMOSD患者出现视神经炎比例为62.5%,AQP4抗体阳性组比例为43.5%,两者差异无统计学意义(P0.05)。三组患者颅内病灶的形态以及部位均无统计学差异(P0.05)。MOG抗体阳性NMOSD患者多为单发长节段脊髓病灶,脊髓病灶数量比MOG抗体阴性组和AQP4抗体阳性组更少,但三组单个脊髓病灶所对应的中位椎体数相近,差异无统计学意义(P0.05)。结论 MOG抗体阳性的NMOSD患者女性比例更高,以复发为主,病程较短,易合并视神经炎,影像学表现与AQP4抗体阳性的NMOSD相比无明显特异性。     

多发性硬化患者抗髓鞘少突胶质细胞糖蛋白抗体的检测及其意义

目的　检测多发性硬化 (MS)患者抗髓鞘少突胶质细胞糖蛋白抗体并探讨其意义。方法　采用EL ISA方法测定 5 6例多发性硬化患者急性期血清和脑脊液配对标本的抗髓鞘少突胶质细胞糖蛋白 (MOG)抗体 ,30例其它神经疾病 (OND)患者为对照。结果　 MS患者血清和脑脊液均可测到抗 MOG抗体 ,血清抗 MOG抗体阳性率为 35 .7% ,脑脊液抗 MOG抗体阳性率为 4 2 .8% ,OND组血清和脑脊液抗 MOG抗体阳性率均为 6 .7% ,与 OND组比较均有显著性意义 (P<0 .0 5 ) ,但血清和脑脊液比较无显著性意义 (P>0 .0 5 )。结论　多发性硬化患者血清和脑脊液中均可检测到抗 MOG抗体 ,可为临床诊断和治疗提供指导。     

脑脊液MOG抗体阳性的视神经脊髓炎谱系疾病患者的临床特征

目的探讨MOG抗体阳性的NMOSD患者的临床特点。方法选择29例NMOSD患者,根据血清AQP-4抗体以及脑脊液MOG抗体检测结果,分为MOG抗体阳性、AQP4抗体阳性的NMOSD(剔除双阳性者),同时选择13例MS患者作为对照。回顾性分析上述三组患者临床信息,统计归纳其临床特点。结果 29例NMOSD患者中血清AQP4抗体阳性者11例,脑脊液MOG抗体阳性者8例。36.4%(4例/11例)AQP4抗体阳性、62.5%(5例/8例)MOG抗体阳性NMOSD患者,以及7.7%(1例/13例)MS患者合并脊髓炎与视神经炎,三组间差异有统计学意义(χ~2=7.128,P=0.028),其中MOG抗体阳性NMOSD患者较MS患者更易合并视神经炎(χ~2=7.289,P=0.014)。MOG抗体阳性NMOSD患者缓解期EDSS分数低于AQP4抗体阳性NMOSD患者[3.50(2.50,4.00),4.00(3.50,6.00),Z=-2.379,P=0.020]。MOG抗体阳性NMOSD脊髓病灶多表现为多发的长节段脊髓病灶,50%(4例/8例)MOG抗体阳性脊髓病灶个数大于1个,与MS组无明显差异,而AQP4抗体阳性组均为单个病灶。MOG抗体阳性NMOSD脊髓病灶长度较AQP4抗体阳性组短[分别(3(2,3)个椎体、4(3,5)个椎体,Z=-2.499,P=0.012],较MS组[(1.25(1,1.5)个椎体]长(Z=-3.447,P0.001)。8例MOG抗体阳性患者中5例存在颅内病灶,3例表现为NMOSD样颅内病灶,余2例表现为MS样颅内病灶,其病灶形态及部位与AQP4抗体阳性组无明显差异,而与MS组存在差异。结论 MOG抗体阳性NMOSD合并视神经炎的患者较多,临床残障程度较轻,预后较好,脊髓病灶为多发的长节段脊髓病灶;颅内病灶的形态及部位与MS无明显差异。     

血清MOG抗体阳性炎性脱髓鞘疾病患者临床特征分析

目的探讨MOG抗体阳性炎性脱髓鞘疾病患者的临床特征。方法回顾性分析36例血清MOG抗体阳性炎性脱髓鞘疾病患者(MOG抗体阳性组)与87例血清AQP4抗体阳性NMOSD患者(AQP4抗体阳性组)的临床信息,分析比较两组患者的临床特征。结果 MOG抗体阳性组与AQP4抗体阳性组患者相比,患病男女比例(1︰1.77 vs.1︰6.25,P=0.005)及发病年龄[(23.17±14.37)岁vs.(35.91±12.91)岁,P=0.000]差异存在统计学意义,两组患者均以女性为多,MOG抗体阳性组患者以儿童和青年为主。MOG抗体阳性组首发脱髓鞘事件中ADEM患者比例高于AQP4抗体阳性组[7例(19.4%)vs.0例(0%),P=0.000],脊髓炎[11例(30.6%)vs.47例(50.4%),P=0.018)]和脑干综合征[5例(13.9%)vs.25例(28.7%),P=0.049)]患者比例低于AQP4抗体阳性组。MOG抗体阳性组患者出现肢体抽搐症状患者比例高于AQP4抗体阳性组[5例(13.9%)vs.0(0%),P=0.002]。影像学表现上,MOG抗体阳性组头部总病灶[27例(75.0%)vs.33例(37.9%)]及NMO非典型病灶[23例(85.2%)vs.4例(12.1%)]患者比例高于AQP4抗体阳性组,头部NMO典型病灶[4例(14.8%)vs.29例(87.9%)]患者比例低于AQP4抗体阳性组(均P=0.000),仅14.8%MOG抗体阳性炎性脱髓鞘疾病患者存在典型NMO头部病灶。MOG抗体阳性组患者截访时EDSS评分低于AQP4抗体阳性组[(2.36±1.66)分vs.(3.83±1.66)分,P=0.000]。结论 MOG抗体阳性炎性脱髓鞘疾病患者男女比例差异较小,与AQP4抗体阳性NMOSD患者相比发病年龄小,首次发作以ADEM、视神经炎及脊髓炎为主,易出现肢体抽搐症状,少见NMO典型头部病灶,倾向于累及下段脊髓,预后较好。     

多发性硬化患者血清维生素D水平变化及与临床相关性研究

目的观察多发性硬化(MS)患者体内维生素D水平,探讨维生素D水平与MS临床表型的关系。方法收集MS患者72例,包括复发缓解型MS(RRMS)62例、继发进展型MS(SPMS)7例及原发进展型MS(PPMS)3例;视神经脊髓炎(NMO)患者24例;以32名健康体检者为健康对照组(NC组)。采用电化学发光法对血清25-羟维生素D_3[25-hydroxyvitamin D_3,25(OH)D_3]进行检测,所有MS患者在留取血标本的同时进行扩展残疾状态量表(EDSS)评分,对其中15例急性复发期RRMS患者在缓解期再次行血清25(OH)D_3检测和EDSS评分。结果 MS组、NC组及NMO组间血清25(OH)D_3水平比较差异有统计学意义(F=10.55,P0.01),MS组及NMO组均低于NC组(分别P0.01,P0.05),但MS组与NMO组相比差异无统计学意义(P0.05);SPMS患者血清25(OH)D_3水平低于NC组(P0.01),但与RRMS患者比较无统计学差异(P0.05);RRMS患者血清25(OH)D_3水平缓解期高于急性复发期(t=2.92,P0.05),但仍低于NC组(P0.01)。结论 MS及NMO患者体内维生素D不足,且维生素D不足贯穿于MS的不同病程阶段,RRMS患者急性复发期维生素D不足更为明显。     

抗髓鞘碱性蛋白抗体及抗髓鞘少突胶质细胞糖蛋白抗体在中枢神经系统炎性脱髓鞘疾病诊断中的价值

目的探讨抗髓鞘碱性蛋白抗体(抗MBP抗体)及抗髓鞘少突胶质细胞糖蛋白抗体(抗MOG抗体)在中枢神经系统炎性脱髓鞘疾病中的表达率,并研究两种抗体对该病的临床诊断价值。方法选取我院于2012-03—2013-09收治的中枢神经系统炎性脱髓鞘疾病患者90例为实验组(MS组30例,AM组30例,NMO组30例);同时选取45例非中枢神经系统炎性疾病患者为对照组。应用ELISA方法对各组患者血清和脑脊液中抗MBP抗体、抗MOG抗体进行检测,并对比分析各组及各亚组之间表达水平差异。结果实验组在血清及CSF中的抗MOG抗体和抗MBP抗体水平均明显高于对照组(P0.05)。而各组的血清抗体阳性率与CSF差异无统计学意义(P0.05)。MS组与AM组血清及CSF中抗MOG抗体阳性率均显著低于NMO组(P0.05)。MS组血清中抗MBP抗体阳性率明显高于AM组(χ2=4.356,P0.05),其余各亚组及CSF中的抗MBP抗体水平均无显著差异(P0.05)。而MS组血清中的抗MBP抗体阳性率显著高于CSF组(χ2=5.963,P0.05)。结论中枢神经系统炎性脱髓鞘疾病患者中抗MBP抗体、抗MOG抗体高表达,对疾病诊断具有临床意义;同时血清中的抗MOG抗体和抗MBP抗体含量差异可辅助疾病各亚型的鉴别诊断。     

多发性硬化患者血清尿酸水平的变化及意义

目的 :探讨多发性硬化 (MS)患者血清尿酸 (UA)水平变化与病情活动性的关系。方法 :比较复发 缓解型MS(relapsing remittingmultiplesclerosis ,RRMS)患者急性期及经大剂量甲泼尼龙 (甲基强的松龙 )冲击治疗后缓解期血清UA值 ,并与其他非炎症性神经系统疾病 (non inflammatoryneurologicaldisease ,NIND)作对照 ,同时对比治疗前后头颅MRI增强检查情况。结果 :RRMS患者急性期血清UA水平显著低于缓解期及NIND组 ,缓解期血清UA值虽低于对照组 ,但差异无显著性。治疗前头颅MRI显示病灶明显强化 ,治疗后强化病灶显著减少 ,同时伴随着UA水平回升 ,临床症状改善。结论 :血清UA水平变化与MS患者病情变化相关 ,UA可作为观察MS病情活动性及激素疗效的指标之一。     

复发-缓解型多发性硬化和化脓性脑膜炎患者血清和脑脊液中IL-18和IFN-γ水平的研究

目的探讨白细胞介素-18(IL-18)、干扰素-γ(IFN-γ)在化脓性脑膜炎(BM)及复发-缓解型多发性硬化(RRMS)发病中的可能的病理生理机制。方法选取RRMS急性期患者24例,BM患者8例及作为对照组的非炎性神经系统疾病(NIND)患者12例,应用ELISA法测定受试者血清及脑脊液中IL-18、IFN-γ水平。结果与NIND组相比,RRMS组血清IL-18水平显著升高,而血清IFN-γ水平无明显差异,但两者间呈显著正相关。脑脊液中IL-18、IFN-γ在RRMS组和NIND组检测到的阳性例数极低,相比之下无统计学差异。与NIND组相比,BM组血清中IL-18水平明显升高,但无统计学差异,而血清中IFN-γ及脑脊液中的IL-18、IFN-γ水平在BM组中均有显著性升高。结论IFN-γ及IL-18参与了多发性硬化及化脓性脑膜炎这两种不同的中枢神经系统炎性疾病的免疫病理生理学机制。     

OCB、抗MBP抗体及抗MOG抗体在中枢神经系统炎性脱髓鞘疾病诊断中的意义

目的：通过观察中枢神经系统炎性脱髓鞘疾病患者寡克隆区带（OCB）、抗髓鞘碱性蛋白（MBP）抗体及抗髓鞘少突胶质细胞糖蛋白（M OG ）抗体的阳性率,为临床诊断提供一定的参考。方法入组91例中枢神经系统炎性脱髓鞘疾病患者为观察组（其中MS 30例,NMO 61例）及50例神经系统非炎性病变患者为对照组。首先分析观察组与对照组间OCB、脑脊液及血清中抗MBP抗体、抗MOG抗体阳性率的差异,再分析观察组中MS亚组及NMO亚组间上述指标阳性率的差异。结果2组比较,OCB、血清抗MBP抗体及血清抗MOG抗体阳性率比较差异有统计学意义（P＜0.05）,脑脊液抗MBP抗体及脑脊液抗MOG抗体阳性率比较差异无统计学意义（P＞0.05）。MS亚组与NMO亚组,OCB、血清抗MBP抗体阳性率比较差异有统计学意义（P＜0.05）,脑脊液抗MBP抗体、血清抗MOG抗体及脑脊液抗MOG抗体阳性率比较差异无统计学意义（P＞0.05）。结论 OCB阳性对诊断MS具有重要意义。血清抗MBP抗体及抗MOG抗体可为中枢神经系统炎性脱髓鞘疾病的诊断提供重要实验室依据,血清抗MBP抗体在MS与NMO的鉴别诊断中具有一定价值。     

CSF levels of soluble HLA-G and Fas molecules are inversely associated to MRI evidence of disease activity in patients with relapsing-remitting multiple sclerosis

Cerebrospinal fluid (CSF) concentrations of soluble human leukocyte antigen class I (HLA-I) (sHLA-I), HLA-G (sHLA-G) and anti-apoptotic Fas (sFas) molecules were measured by enzyme linked immunosorbent assay technique in 65 relapsing-remitting (RR) MS patients classified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Sixty-four patients with other inflammatory neurological disorders (OIND) and 64 subjects with noninflammatory neurological disorders (NIND) served as controls. CSF concentrations were higher in RRMS and in OIND than in NIND patients for sHLA-I (P < 0.02), greater in RRMS than in OIND and in NIND for sHLA-G (P < 0.001 and P < 0.01, respectively) and lower in RRMS than in OIND and in NIND for sFas (P < 0.001 and P < 0.02, respectively). An increase in CSF levels was identified in MRI active RRMS for sHLA-I (P < 0.01) and in MRI stable RRMS for sHLA-G (P < 0.01), whereas CSF values of sFas were decreased in RRMS without Gd-enhancing lesions (P < 0.02). In MS patients with no evidence of MRI disease activity, a trend towards an inverse correlation was found between CSF concentrations of sHLA-G and sHLA-I and between CSF levels of sHLA-G and sFas. Our results indicate that enhanced CSF levels of sHLA-I antigens most likely represent an indirect manifestation of intrathecal immune activation taking place in neuroinflammation. Conversely, reciprocal fluctuations in CSF sHLA-G and sFas levels observed when MRI disease activity resolved suggest that sHLA-G could play an immunomodulatory role in MS through Fas/FasL-mediated mechanisms.     

Antibodies against myelin oligodendrocyte glycoprotein in the cerebrospinal fluid of multiple sclerosis patients

Antibodies against myelin oligodendrocyte glycoprotein (MOG) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) in different animal species and are implicated in the immunopathogenesis of multiple sclerosis (MS). In order to evaluate the anti-MOG response, we have analyzed the cerebrospinal fluids (CSFs) from 44 MS patients and 51 controls, 11 with other inflammatory neurological disorders (OIND) and 40 with non-inflammatory neurological disorders (NIND). The frequency of anti-MOG antibodies positive patients in the MS group (30%) was significantly higher compared to the NIND (8%, p=0.02), but not compared to the OIND group (55%, p=0.228). Interestingly, all six patients with neurosarcoidosis had MOG-specific antibodies in their CSF. Frequency of anti-MOG antibodies was similar in patients with clinically active and stable MS (32% and 26%, respectively; p=0.921). However, in clinically active MS patients, antibody titers were higher in comparison with patients with stable disease, although the difference did not reach the level of statistical significance (p=0.06). These results further support the potential role of anti-MOG antibodies in the immunopathology of MS in the subset of patients with this disease. Furthermore, our findings suggest for the first time that anti-MOG antibodies could be an accessory diagnostic tool in neurosarcoidosis.     

Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis

OBJECTIVE: Myelin oligodendrocyte glycoprotein (MOG) is a highly immunogenic minor component on the outside surface of CNS myelin which is believed to be one of the autoantigens in multiple sclerosis. The aim of this study was to evaluate the diagnostic potential of anti-MOG IgG antibody levels in cerebrospinal fluid (CSF) and serum of patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and non-inflammatory neurological diseases (NIND) as markers for the different clinical types of multiple sclerosis. PATIENTS AND METHODS: Consecutive serum and cerebrospinal fluid samples were taken from 21 patients with RRMS, 7 patients with PPMS and 19 patients with NIND. The antibody responses to MOG were determined in paired samples of these different clinical groups by enzyme-linked immunoassay using a recombinant human MOG protein. RESULTS: The performed analysis indicated that the differences in levels of anti-MOG IgG antibody in serum and cerebrospinal fluid from the patients with RRMS, PPMS or NIND were not statistically significant. CONCLUSION: The assay is not sensitive or specific enough to be used as a differential diagnostic tool for the clinical types of MS, nor for MS itself.     

Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms

The purpose of this study was to provide further insight into the effective relevance of the association between Chlamydia pneumoniae and MS. We evaluated by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 46 relapsing-remitting (RR), 14 secondary progressive (SP) and 11 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Fifty-one patients with other inflammatory neurological disorders (OIND) and 52 with non-inflammatory neurological disorders (NIND) were used as controls. A C. pneumoniae-specific intrathecal IgG synthesis as detected by the relative specific index was present in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was significantly more frequent in MS and in OIND than in NIND (p<0.001) and in SP and PP MS than in RR MS patients (p<0.02). Among the patients with C. pneumoniae-specific intratecally produced antibodies, CSF high-affinity anti-C. pneumoniae IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in RR MS and NIND patients. These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNS) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecal production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role.     

Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing-remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings

We have investigated the presence of non-classical soluble HLA-G molecules (sHLA-G) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and the possible relationships between CSF levels of sHLA-G, classical soluble HLA-I (sHLA-I) molecules, IL-10 amounts and Magnetic Resonance Imaging (MRI) findings were evaluated. We studied by ELISA technique the sHLA-I, sHLA-G and IL-10 levels in CSF of 50 relapsing-remitting (RR) MS patients stratified according to clinical and MRI evidence of disease activity. Thirty-six patients with other inflammatory neurological disorders (OIND) and 41 with non-inflammatory neurological disorders (NIND) were used as controls. CSF mean levels were significantly higher in MS and OIND than in NIND for sHLA-I (p<0.001) and in MS than in controls for sHLA-G (p<0.001), with no differences among the various groups for IL-10 mean concentrations. An increase in CSF sHLA-I was found in MS patients with Gd-enhancing lesions (p<0.01), while sHLA-G and IL-10 were more represented in MS patients without lesional activity on MRI scans (p<0.02). In MRI-inactive MS, CSF IL-10 mean concentrations were significantly greater in patients with CSF-detectable levels of sHLA-G than in those without any evidence of CSF sHLA-G expression (p<0.05). Our findings suggest that CSF classical sHLA-I and non-classical sHLA-G levels may modulate MS activity as assessed by MRI acting in opposite directions. The association observed between sHLA-G and IL-10 when Gd-enhancing lesion resolved indicates a potential immunoregulatory role for IL-10 in the control of MS disease activity by shifting the sHLA-I/sHLA-G balance towards sHLA-G response.     

Biological markers in cerebrospinal fluid for axonal impairment in multiple sclerosis: acetylcholinesterase activity cannot be considered a useful biomarker

An impairment of the cholinergic system activity has been demonstrated in multiple sclerosis (MS). The correlation between the cholinergic system and the cognitive dysfunction in MS has led to studies on the use of acetylcholinesterase inhibitors (AChEI). The acetylcholinesterase (AChE), essential enzyme for the regulation of turnover of acetylcholine, can be considered the most important biochemical indicator of cholinergic signaling in the nervous system. Besides its catalytic properties, AChE has a crucial role in the regulation of the immune function. Based on the role of the AChe in the regulation of cholinergic signaling in the nervous system, the aim of the present study is to evaluate the activity of AChE in different pathological conditions: MS, other inflammatory neurological disorders (OIND) and non-inflammatory neurological disorders (NIND). We measured AChE activity in CSF samples obtained from 34 relapsing–remitting MS patients and, as controls, 40 patients with other inflammatory neurological disorders (OIND) and 40 subjects with other non-inflammatory neurological disorders (NIND). Fluorimetric detection of the AChE in MS patients and in the controls showed no statistically significant differences: 1.507 ± 0.403 nmol/ml/min in MS patients, 1.484 ± 0.496 nmol/ml/min in OIND and 1.305 ± 0.504 nmol/ml/min in NIND. Similar results were obtained in another recent study, using a different method. Further studies must be conducted on a larger number of patients, with different degrees of cognitive impairment. However, AChE measured in CSF can probably not be considered a useful biomarker for the assessment of the functional alterations of cholinergic system in pathological conditions.     

Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P < 0.05, < 0.02 and < 0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P < 0.01) and OIND (P < 0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P < 0.001, < 0.001 and < 0.05, respectively) and MRI (P < 0.001, < 0.001 and < 0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P < 0.02 and < 0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.     

Secondary lymphoid organ chemokines are elevated in the cerebrospinal fluid during central nervous system inflammation

Secondary lymphoid organ chemokines have been implicated in chronic inflammation. Their expression in the central nervous system (CNS) has not been studied. Here, levels of secondary lymphoid organ chemokines CCL19 (Exodus-3, MIP-3beta), CCL21 (Exodus-2, 6Ckine, SLC) and CXCL12 (SDF-1alpha) were analysed by ELISA in cerebrospinal fluid (CSF) and plasma from patients with multiple sclerosis (MS); acute optic neuritis (ON) with oligoclonal IgG in the CSF (i.e., first bout of MS); acute ON without oligoclonal IgG (non-MS-type ON); other inflammatory neurological diseases (OIND); and non-inflammatory neurological diseases (NIND). NIND CSF contained CCL19 and CXCL12, while CCL21 was not detected. Intrathecal production of CCL19 and CCL21 was elevated in MS, MS-type ON, and OIND, but not in non-MS-type ON. In MS, CSF levels of CCL19 weakly correlated with CSF cell counts. Intrathecal production of CXCL12 was elevated only in OIND. The role of elevated CCL19 and CCL21 in MS could be retention of mature dendritic cells (DC) in the CNS, recruitment of nai;ve T cells and activated B cells, as well as de novo formation of secondary lymphoid structures in MS plaques.     

Chlamydia pneumoniae—specific intrathecal oligoclonal antibody response is predominantly detected in a subset of multiple sclerosis patients with progressive forms

The purpose of this study was to verify the actual involvement of Chlamydia pneumoniae in multiple sclerosis (MS) by the evaluation of its specific intrathecal humoral immune response in MS. We measured by enzyme-linked immunosorbent assay (ELISA) technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae immunoglobulin G (IgG) in 27 relapsing-remitting (RR), 9 secondary progressive (SP), and 5 primary progressive (PP) MS patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Twenty-one patients with other inflammatory neurological disorders (OIND) and 21 with noninflammatory neurological disorders (NIND) were used as controls. Quantitative intrathecal synthesis of anti-C. pneumoniae IgG was determined by antibody-specific index (ASI), whereas the presence of C. pneumoniae—specific CSF oligoclonal IgG bands was assessed by antigen-specific immunoblotting. ASI values indicative of C. pneumoniae—specific intrathecal IgG synthesis were present in a small proportion of MS (29.3%), OIND (33.3%), and NIND (4.8%) patients and were significantly more frequent (P <.05) in total MS and in OIND than in NIND and in SP (P <.01) and PP MS (P <.05) than in RR MS. C. pneumoniae—specific CSF-restricted OCB were detected only in three SP, one PP, and one RR MS patients. These findings suggest that an intrathecal production of anti-C. pneumoniae IgG is part of humoral polyreactivity driven by MS chronic brain inflammation. However, an intrathecal release of C. pneumoniae—specific oligoclonal IgG can occur in a subset of patients with MS progressive forms in whom a C. pneumoniae— persistent brain infection may play a pathogenetic role.     

Cerebrospinal fluid molecular demonstration of Chlamydia pneumoniae DNA is associated to clinical and brain magnetic resonance imaging activity in a subset of patients with relapsing-remitting multiple sclerosis

To further explore the link between Chlamydia pneumoniae and multiple sclerosis (MS), we examined cerebrospinal fluid (CSF) samples from 71 patients with MS and from 72 patients suffering from other inflammatory neurological disorders (OIND) or noninflammatory neurological disorders (NIND). All samples were analysed by a touchdown nested polymerase chain reaction (n-PCR) for C. pneumoniae with primer sets which amplify target sequence genes encoding the major outer membrane protein (MOMP), the 16S rRNA and the Hsp-70 protein. A molecular study was also performed to evaluate genetic diversity among isolates of C. pneumoniae and to compare chlamydial sequences. PCR was found positive in 36.6% of total MS, in 28.1% of OIND and in 37.5% of NIND patients, without any statistical differences among the various groups examined. CSF PCR evidence of C. pneumoniae was significantly more frequent in relapsing-remitting (RR) than in secondary progressive (SP) (P < 0.001) and in primary progressive (PP)MS (P < 0.05), in clinically active than in clinically stable MS (P < 0.05) and in MRI active than in MRI inactive MS (P < 0.001). The analysis of CSF expression of each single C. pneumoniae-specific gene revealed that detectable levels of MOMP were significantly more frequent in MS patients with relapse (P < 0.05), whereas PCR positivity for MOMP and 16S rRNA genes were more represented in MS patients with clinical and MRI evidence of disease activity (P < 0.05). Similar rates for MOMP and 16S rRNA genes were detected in CSF of both MS patients and controls, whereas CSF PCR positivity for Hsp-70 gene was observed in only three active RR MS patients. Sequence analysis revealed significant homologies with C. pneumoniae compared to other Chlamydial spp. These findings confirm that the C. pneumoniae detection within the central nervous system (CNS) is not selectively restricted to MS, but accounts in a variety of neurological diseases. In addition, our results suggest that CSF C. pneumoniae-specific DNA detection can occur in a subset of MS patients with clinical and MRI active RR form in whom a C. pneumoniae brain chronic persistent infection may play a significant role in the development of disease.