Guillain-Barré综合征患者中枢神经系统内源性免疫反应与脑脊液蛋白的相关性

目的探讨Guillain-Barré综合征(GBS)患者CNS内源性免疫反应与CSF蛋白的关系及临床意义。方法收集69例GBS患者的临床资料,采用免疫散射比浊法测定CSF和血清免疫球蛋白G(Ig G)、白蛋白水平,计算CSF白蛋白/血清白蛋白(QALB)、Ig G指数、24 h鞘内Ig G合成率。结果 CSF蛋白正常与偏高患者性别、年龄、残疾量表评分、上呼吸道感染、胃肠感染、肺部感染、近期疫苗接种比率差异无统计学意义。CSF蛋白正常患者CSF蛋白、QALB、Ig G、24 h鞘内Ig G合成率均显著低于CSF蛋白异常患者(均P0.01),Ig G指数差异无统计学意义。24 h鞘内Ig G合成率正常患者CSF蛋白[0.49(10.84)]g/L显著低于偏高患者[0.98(12.97)]g/L(U=205.50,P0.01)。24 h鞘内Ig G合成率与CSF蛋白呈正相关(r=0.599,P0.01)。结论 GBS患者CSF蛋白水平随CNS内源性免疫反应增强而增加,24 h鞘内Ig G合成率有助于GBS的病情监测及预后评估。     

Guillain-Barré综合征患者脑脊液和血清S-100b蛋白含量的测定

目的探讨脑脊液和血清S-100b蛋白含量对Guillain-Barre综合征(GBS)患者施万细胞损伤的评估价值.方法采用酶联免疫吸附试验双抗体夹心法对50例GBS患者(重型组19例,轻型组31例)和22名正常人的脑脊液和血清S-100 b蛋白含量进行检测,同时行脑脊液细胞学检查.对GBS患者还进行了脑脊液和血清的动态检测.结果 (1) 两组GBS患者脑脊液 S-100b蛋白含量均高于对照组(均P<0.01),重型组与轻型组差异亦有显著意义(P<0.01);血清S-100b蛋白含量重型组患者高于轻型组和对照组(均P<0.05),轻型组与对照组差异无显著意义(P＞0.05).(2)重型组患者脑脊液单核细胞比例明显高于轻型组和对照组(均P<0.01),轻型组与对照组间差异无显著意义(P＞0.05).(3)GBS患者脑脊液 S-100b蛋白含量随脑脊液单核细胞比例增减及病情的轻重而发生相应的变化.结论脑脊液和血清 S-100b蛋白含量与GBS患者病情严重程度相关.     

Guillain-Barr综合征患者脑脊液和血清S-100b蛋白含量的测定

目的　探讨脑脊液和血清S 10 0b蛋白含量对Guillain Barre综合征 (GBS)患者施万细胞损伤的评估价值。方法　采用酶联免疫吸附试验双抗体夹心法对 5 0例GBS患者 (重型组 19例 ,轻型组 31例 )和 2 2名正常人的脑脊液和血清S 10 0b蛋白含量进行检测 ,同时行脑脊液细胞学检查。对GBS患者还进行了脑脊液和血清的动态检测。结果　 (1)两组GBS患者脑脊液S 10 0b蛋白含量均高于对照组 (均P <0 0 1) ,重型组与轻型组差异亦有显著意义 (P <0 0 1) ;血清S 10 0b蛋白含量重型组患者高于轻型组和对照组 (均P <0 0 5 ) ,轻型组与对照组差异无显著意义 (P >0 0 5 )。 (2 )重型组患者脑脊液单核细胞比例明显高于轻型组和对照组 (均P <0 0 1) ,轻型组与对照组间差异无显著意义(P >0 0 5 )。 (3)GBS患者脑脊液S 10 0b蛋白含量随脑脊液单核细胞比例增减及病情的轻重而发生相应的变化。结论　脑脊液和血清S 10 0b蛋白含量与GBS患者病情严重程度相关。     

格林—巴利综合征患者血清TNF和sIL—2R水平

目的:探讨肿瘤坏死因子(TNF)和可溶性白细胞介素2受体(sIL-2R)在格林-巴利综合征(GBS)发病中的作用及其临床意义。方法:采用双抗体夹心ELISA法对28例GBS患者和36例正常对照血清TNF及sIL-2R水平进行了检测。结果:GBS组血清TNF及sIL-2R水平显著高于正常对照组,血清TNF及sIL-2R水平变化与GBS病情及预后密切相关,恢复期血清TNF及sIL-2R水平显著降低。结论:TNF及sIL-2R参与了GBS的发病过程,检测血清TNF及sIL-2R水平对判定GBS病情及预后有一定的临床意义。     

吉兰-巴雷综合征患者血清和脑脊液中P2蛋白抗体检测及其临床意义

目的评价P2蛋白抗体在辅助吉兰-巴雷综合征(GBS)临床诊断中的价值.方法用ABC-ELISA方法检测64例血清和CSF配对的GBS病人样品中IgG和IgM型P2抗体水平.结果 GBS患者CSF中IgM型P2抗体阳性率明显高于其它神经系统疾病组和正常对照组(P＜0.01),且重症型GBS病人高于轻症型病人(P=0.0019),血清与CSF间P2抗体水平无相关性.结论 GBS病人CSF中存在P2特异性免疫球蛋白,CSF中IgM型P2抗体检测有助于辅助GBS的临床诊断和病情评价.     

多发性硬化患者脑脊液和血清中髓鞘碱蛋白和白介素-16的相关研究

目的　了解多发性硬化 (MS)患者脑脊液 (CSF)和血清髓鞘碱性蛋白 (MBP)和白介素 16 (IL 16 )的水平 ,探讨两者之间的相关性 ,及其在MS发病过程中的作用。方法　采用ELISA法对 31例MS患者CSF和血清的MBP和IL 16进行测定 ,并与 2 4例炎性脱髓鞘性多发性神经病 (IDP)、2 2例对照者进行比较。结果　MS组CSF和血清中的MBP水平均显著高于IDP组及对照组 (均P <0 .0 1) ;CSF中的IL 16的水平显著高于对照组 (P <0 .0 1) ,而血清中IL 16水平与对照组相比无明显差异 (P >0 .0 5 )。MS组中CSF的MBP水平与IL 16水平显著相关 (r=0 .4 6 8,P <0 .0 1) ,但血清中MBP的水平与IL 16水平无相关性 (r=- 0 .131,P >0 0 5 ) ;CSF中MBP水平和血清中MBP的水平有相关性 (r=0 .5 0 5 ,P <0 .0 1) ,CSF中IL 16和血清中IL 16的水平无相关性 (r=0 .0 2 2 ,P >0 .0 5 )。结论　MBP是诱导MS发病的主要自身抗原之一 ,MBP可能主要在中枢神经系统中刺激IL 16的产生 ;而IL 16主要在中枢神经局部产生并起作用     

多发性硬化患者脑脊液一氧化氮水平的检测及意义

目的探讨多发性硬化患者脑脊液(CSF)一氧化氮(NO)含量变化.方法采用硝酸还原酶法检测43例多发性硬化(MS)患者、25例吉兰-巴雷综合症(GBS)患者及39例对照者CSF的NO水平,同时进行其生化和细胞学成分及寡克隆IgG区带(IgG-OB)分析.结果MS组CSF的NO水平明显高于对照组(P＜0.01).结论硝酸还原酶法能快速、准确地检测CSF的NO含量;NO参与了MS的免疫发病机制,并在一定程度上反映机体细胞免疫的状态.     

格林-巴利综合征患者血清及脑脊液中GM1抗体及IgG指数检测

检测了19例格林－巴利综合征（GBS）患者血清和脑脊液（CSF）中神经节苷酯1（GM１）－IgG抗体和lgG－指数，并与11例对照组比较。结果显示，GBS组GM1－IgG抗体滴度及IgG-指数均明显高于对照组，并在1例复发型GBS患者血清中检测出高水平GM1－IgG抗体。提示GM1可能是GBS相关抗原。GBS患者IgG-指数增高可能反映CSF中免疫活性细胞的激活。GM1－IgG抗体是否可作为GBS复发的标志尚待进一步验证。     

Guillain-Barré综合征患者血清和脑脊液IL-18、IL-13水平的测定及临床意义

目的探讨IL-18、IL-13在吉兰-巴雷(GBS)患者血清和脑脊液(CSF)中的含量变化及其在发病机制中的作用。方法用酶联免疫吸附法(ELISA)测定GBS患者急性期与恢复期血清及脑脊液IL-18、IL-13水平。结果GBS患者急性期血清及脑脊液IL-18与IL-13水平均明显高于恢复期和对照组(均P<0·01);且病情重者高于病情轻者(均P<0·05);恢复期血清IL-18、IL-13水平虽下降,但仍高于对照组(均P<0·01);相关分析发现血清和脑脊液IL-18、IL-13呈正相关关系(均P<0·05)。结论IL-18、IL-13可能在周围神经脱髓鞘的病理损害的发病机制中起着十分重要的作用,并与病情轻重有关。     

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。     

Tumor necrosis factor and interleukin-1 in the CSF and sera of patients with multiple sclerosis

Serum and cerebrospinal fluid (CSF) from 31 patients with multiple sclerosis (MS) were examined to determine the levels of tumor necrosis factor (TNF) and interleukin (IL)-1 alpha (or IL-1 beta) by an enzyme-linked immunosorbent assay. TNF was detected in 29 (93.5%) of CSF from 31 cases of MS. TNF was also detectable in 100% of CSF from patients with acute relapsing MS in exacerbation. Patients with acute relapsing MS in exacerbation showed significantly higher CSF levels of TNF as compared with either those in remission or the controls (P less than 0.001 and P less than 0.0001, respectively). Increased levels of TNF were also detected in 35.5% of the MS sera, and especially in those with acute relapsing MS in exacerbation. Increased TNF levels were also frequent in the CSF and sera of patients with Guillain-Barré syndrome (GBS), which is also a demyelinating disease. No IL-1 alpha (or IL-1 beta) was detected in either CSF or sera of 31 MS patients. It is considered likely that TNF CSF levels may reflect disease activity in MS.     

Increased levels of soluble tumor necrosis factor receptor in patients with multiple sclerosis and HTLV-1-associated myelopathy

Tumor necrosis factor-α (TNF-α) is a potent mediator produced by activated T lymphocytes and macrophages, which may play a role in the pathogenesis and development of multiple sclerosis (MS) and HTLV-1-associated myelopathy (HAM). The first step in the induction of many biological effects elicited by TNF-α is its binding to specific cell surface receptors. A soluble form of TNF receptors (sTNF-R) can be detected in the body fluid. We measured sTNF-R levels in the sera and cerebrospinal fluid (CSF) of patients with either MS or HAM, and evaluated the correlation between this mediator and diseaseaactivity. The levels of sTNF-R in the sera and CSF of patients with MS were significantly increased compared with controls, particularly patients with acute relapsing MS during an exacerbation (P < 0.001). CSF levels of sTNF-R showed a strong correlation with those of TNF (r = 0.716, P < 0.001). Higher levels of sTNF-R in the sera of HAM patients were detected as compared with those of either controls (P < 0.001) or non-HAM carriers (P < 0.001). Patients with HAM exhibited significantly higher CSF levels of sTNF-R than those with other neurological diseases (P < 0.0001). These results suggest that the detection of sTNF-R in the sera and CSF may predict disease progression. Availability of such a marker wou ld be useful in monitoring disease activity.     

Soluble complement receptor type 1 in serum and cerebrospinal fluid of patients with Guillain-Barré syndrome and multiple sclerosis

Activation of complement is critically involved in inflammatory reactions in both Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). Soluble human complement receptor 1 (sCR1) blocks complement activation by both classical and alternative pathways. We studied serum and cerebrospinal fluid (CSF) concentrations of sCR1 in 23 patients with GBS, 27 patients with MS and 30 controls. No significant differences were found between patients and controls. Transient liver affection probably caused high serum sCR1 levels in two patients with GBS. The serum and CSF sCR1 levels were not correlated to the disease activity of GBS and MS, nor to the relapsing-remitting or chronic-progressive forms of MS. In GBS the CSF sCR1 levels correlated with the CSF total protein concentrations (r = 0.9, P < 0.01), suggesting that sCR leaks from serum into CSF via a damaged blood-nerve barrier. The serum sCRl levels in GBS were slightly higher than in MS (P < 0.05). Whether this reflects changes in the release or consumption of sCR in these patients is at present unknown.     

Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis

Interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF alpha), and IL-6 are cytokines which mediate cellular responses during immune activation and inflammation. In multiple sclerosis (MS) they might be responsible for T-cell activation (IL-1 beta), for demyelination (TNF alpha), and for immunoglobulin (Ig) synthesis (IL-6) within the central nervous system. We studied IL-1 beta, TNF alpha, and IL-6 levels in the cerebrospinal fluid (CSF) of 34 patients with MS, 43 patients with non-inflammatory neurological diseases (NIND), and 19 patients with inflammatory neurological diseases (IND). IL-6 was found in the CSF of 29% of MS, 7% of NIND, and 47% of IND patients. TNF alpha was detected in the CSF of 23% of MS, 7% of NIND, and 29% of IND. CSF IL-6 and TNF alpha levels were significantly higher in MS and IND than in NIND. IL-1 beta was rarely detected in the CSF of any group. At least one cytokine was detected in 52% of MS CSF, 11% of NIND CSF, and 64% of IND CSF. In MS patients, no relationship was observed between the incidence or the amount of intrathecal IgG synthesis or oligoclonal bands and the presence of any cytokine. We also evaluated cytokine levels in paired sera from 11 MS and 13 NIND patients. Low levels of IL-6 were detected in most sera from MS and NIND patients. TNF alpha was detected in only two MS sera, and IL-1 beta was undetectable in any sample. Our results indicate that increased CSF levels of the cytokines IL-6 and TNF alpha occur frequently in MS and IND, but there is no obvious relationship to intrathecal Ig synthesis.     

The soluble 60-kDa tumour necrosis factor receptor: no difference found between patients with relapsing-remitting multiple sclerosis and controls: increasing levels are associated with the recovery from Guillain-Barré syndrome

We determined serum and cerebrospinal fluid (CSF) levels of the soluble 60-kDa tumour necrosis factor (TNF) receptor (sTNF-R p60) in 50 patients with relapsing-remitting multiple sclerosis (MS) and in 18 patients with Guillain-Barré syndrome (GBS). Neither in serum nor in CSF samples was there a statistically significant difference between mean receptor concentrations of patients with MS (serum: 1064, SD 262 pg/ml; CSF: 555, SD 130 pg/ml), with other noninflammatory neurological diseases (serum: 1008, SD 248 pg/ml; CSF: 530, SD 112 pg/ml) and with healthy control subjects (serum: 918, SD 180 pg/ml). In order to determine disease activity, magnetic resonance imaging (MRI) of the brain was performed in all MS patients. The mean sTNF-R p60 levels of patients who showed gadolinium DTPA enhancement on MRI were not different from those without enhancement (1034, SD 274 pg/ml vs 1099, SD 248 pg/ml in serum samples and 546, SD 109 pg/ml vs 565, SD 152 pg/ml in CSF samples). In GBS, the sTNF-R p60 levels of serum and CSF samples were significantly higher than in MS and all control groups except for the group with viral meningitis (VM) (GBS: 1544, SD 834 pg/ml in serum, 882, SD 147 pg/ml in CSF; VM: 1518, SD 375 pg/ml in serum, 1131, SD 611 pg/ml in CSF; P < 0.001 for serum samples and P < 0.005 for CSF samples). Serial serum sTNF-R p60 measurements in 13 patients with GBS showed an increase in receptor levels parallel with the recovery from the disease (1276, SD 374 pg/ml at the time of disease onset, 1554, SD 482 pg/ml 14–24 days later and 1787, SD 525 pg/ml after 28–32 days). From our results and the conflicting data of previous studies, we could not agree with the suggestion that the assessment of sTNF-R p60 in MS patients is a useful marker for disease activity. In GBS, subsequently increasing sTNF-R p60 levels are associated with recovery from the disease. It remains to be shown whether they might represent a relevant pathogenetic factor during this stage of GBS. Received: 31 October 1997 Received in revised form: 26 January 1998 Accepted: 10 February 1998     

Increased levels of soluble vascular cell adhesion molecule-1 ( VCAM-1) in the cerebrospinal fluid and sera of patients with multiple sclerosis and human T lymphotropic virus type-1-associated myelopathy

We evaluated the relationship between the soluble form of vascular cell adhesion molecule-1 (sVCAM-1) and disease activity in patients with multiple sclerosis (MS) or with human T lymphotropic virus type 1-associated myelopathy (HAM), and measured levels of sVCAM-1 in their cerebrospinal fluid (CSF) and sera. Serum and CSF levels of sVCAM-1 were significantly increased in patients with acute relapsing MS during an exacerbation (P < 0.01 and P < 0.001), as well as in chronic progressive MS (P < 0.05 and P < 0.001), compared with healthy individuals and patients with other neurological diseases, respectively. Patients with acute relapsing MS during an exacerbation also exhibited significantly higher serum and CSF levels of sVCAM-1 vs. patients with acute relapsing MS in remission (P < 0.001). Significantly higher serum levels of sVCAM-1 were observed in patients with HAM vs. either healthy individuals (P < 0.01) or non-HAM carriers (P < 0.01). These results suggest that the determination of sVCAM-1 in the sera and CSF may be useful in monitoring the activity of MS and HAM.     

多发性硬化患者外周血和脑脊液淋巴细胞亚群的观察

用碱性磷酸酶抗酸酶法检查了４６例多发性硬化活动期患者外周血和脑脊液的淋巴细胞亚群。结果显示：活动期ＭＳ者外周血ＣＤ＾＋４，ＣＤ＾＋９细胞较对照组减少，ＣＤ＾＋２５细胞，ＣＤ＾＋４／ＣＤ＾＋８比值较对照组升高。ＣＳＦ中ＣＤ＾４，ＣＤ＾＋２５细胞，ＣＤ＾＋４／ＣＤ＾＋８比值较对照组升高，ＣＤ＾＋８细胞降低，且ＣＳＦ中淋巴亚群均高于自身外周血中的相应细胞。     

吉兰-巴雷综合征患者血清和脑脊液抗神经节苷脂抗体检测的意义

目的通过测定吉兰-巴雷综合征(Guillain-BarréSyndrome,GBS)患者血清和脑脊液中抗神经节苷脂GM1抗体水平,探讨其临床意义。方法应用ELISA法检测44例GBS患者血清和脑脊液中抗GM1抗体水平。结果 (1)GBS组血清和脑脊液中抗GM1-IgG抗体水平与其他神经疾病(OND)组、正常对照(NC)组相比有显著性差异(P<0.05);血清中抗GM1-IgM抗体与NC组相比有显著性差异(P<0.05),但与OND组相比无显著性差异(P>0.05);脑脊液中抗GM1-IgM抗体与OND组、NC组相比有显著性差异(P<0.05)。(2)轻重型GBS患者血清和脑脊液中抗GM1抗体的阳性率差异无显著性(P>0.05)。(3)急性炎性脱髓鞘性多发性神经根神经病(AIDP)患者血清和脑脊液中抗GM1抗体阳性率与急性运动轴索型神经病(AMAN)及急性运动感觉轴索型神经病(AMSAN)中抗GM1抗体阳性率者相比无显著性差异(P>0.05)。结论抗GM1抗体可能在吉兰-巴雷综合征的发病中起重要作用,但抗体水平与疾病严重程度无关。     

Expression of TNFα and TGFβ1 in Guillain–Barré syndrome: correlation of a low TNFα-/TGFβ1-mRNA ratio with good recovery and signs for immunoregulation within the cerebrospinal fluid compartment

In the pathogenesis of Guillain-Barré syndrome (GBS) a dysregulation of cytokines is supposed. The protein concentration and mRNA expression of TNFalpha and TGFbeta1 were investigated in cerebrospinal fluid (CSF) and blood in 10 patients with GBS. TNFalpha-mRNA was increased at the beginning of the disease and demonstrated a decline during the time course (P = 0.001). The level of TNFalpha protein was elevated in only a few patients. TGFbeta1-mRNA (P = 0.001) and the active TGFbeta1 protein (P < 0.05) increased during the course of GBS, and the level of total TGFbeta1 protein was temporarily elevated (P = 0.005). A low ratio of TNFalpha-/TGFbeta-mRNA expression correlated to a good clinical course (P < 0.05). The results indicate an association of TNFalpha with disease activity. TGFbeta1 seems to terminate and limit the inflammatory reactions and to promote the healing course of GBS. In addition the investigations show that in GBS immunoregulatory mechanisms also take place in the CSF compartment itself and that CSF cells are involved in the production of pro-inflammatory as well as immunosuppressive cytokines.