T淋巴细胞受体与多发性硬化

免疫性T淋巴细胞在多发性硬化(MS)的发病中有重要地位,国外关于MS患者T淋巴细胞受体β链可变区的研究显示MS患者T淋巴细胞受体β链可变区的某些区段会有克隆性扩增,并且与临床类型、病程、MRI表现、扩展残疾状态评分有一定关系.本文就MS患者T淋巴细胞受体β链可变区的表现进行综述.     

多发性硬化的轴索损害

多发性硬化不仅有脱髓鞘性损害 ,还有轴索损害 ,且轴索损害与患者的功能缺损进展有关。轴索损害与炎症反应有一定关系 ,还有其他机制。认识轴索损害的存在并试图防止轴索损害有可能延缓功能缺损的进展     

雷公藤片对多发性硬化患者外周血T淋巴细胞亚群的影响

目的　探讨雷公藤对多发性硬化 (MS)的免疫调节机制。方法　将 4 2例MS患者随机分为雷公藤治疗组及非雷公藤治疗组 ,观察两组治疗前后及 2 0例正常对照者外周血T淋巴细胞亚群分布。结果　雷公藤治疗及非雷公藤治疗的MS组治疗前其外周血中CD3 、CD8 细胞较正常对照组明显降低 ,CD4 与正常对照组比较差别无显著性 ,CD4 CD8 比值较正常对照组显著升高 ;雷公藤治疗组治疗前后外周血中CD3 无明显差别 ,CD4 较治疗前明显降低 ,CD8 明显增加 ,CD4 CD8 比值则显著降低 ,而非雷公藤治疗组治疗前后外周血CD3 、CD4 、CD8 、CD4 CD8 比值无显著性变化。结论　雷公藤治疗MS的免疫抑制机制可能是通过调节T淋巴细胞亚群分布而发挥作用     

神经髓鞘及脱脂神经髓鞘诱导MS-TCL增殖反应比较

目的 比较神经髓鞘和脱脂神经髓鞘诱导多发性硬化(MS)T淋巴细胞系(TCL)对11种神经髓鞘成份的增殖反应。方法 以2种人神经髓鞘在体外二次致敏,诱导MS-TCL和正常人TCL,用MBP、PLP及其合成多肽等抗原检测PTL的增殖反应。结果 与非脱脂TCL相比,脱脂髓鞘使MS组的免疫反应性显著改变。尤其对PLP6种多肽反应性的改变有统计学差异,总平均阳性孔比较P<0.001(3.41±4.83 vs 5.49±5.31)。结论 髓鞘脱脂使MS组增殖反应显著增加,二组的差别更明显。提示在髓鞘脱脂方面MS和正常人反应的异质性,此点对理解MS的病理机制可能很重要。     

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。     

miRNA对多发性硬化CD4+T淋巴细胞分化调控机制的研究进展

多发性硬化(MS)是一种免疫介导的中枢神经系统慢性炎性脱髓鞘性疾病.CD4+T细胞在MS的发病机制中具有重要作用.微小RNA(miRNA)是一类具有调控活性的内源性非编码小分子RNA,通常在转录后水平调控靶基因的表达.miRNA对MS中CD4+T细胞的增殖、分化和功能维持发挥特定的调控作用,当miR-NA表达异常时可能...     

多发性硬化患者髓鞘特异性抗体的研究进展

多发性硬化是中枢神经系统炎症性脱髓鞘性自身免疫性疾病,自身髓鞘蛋白抗体在其免疫学发病机制中扮演着重要角色。多发性硬化患者体液中存在多种髓鞘蛋白抗体。本文对此进展及其与临床的关系进行介绍。     

火把花根片对多发性硬化患者外周血T淋巴细胞亚群的影响

多发性硬化 ( Multiple sclerosis,MS)是一种免疫所介导的、选择性损害中枢神经系统白质的自身免疫性疾病 ,迄今为止其病因和发病机制尚不完全清楚 ,其临床特点主要为神经功能的缺失 ,表现出缓解复发、缓慢进行性加重的特点 ,目前尚无肯定有效的防治措施 [1 ] 。火把花根片是一种目前临床应用较多的用于治疗类风湿性关节炎、红斑狼疮等自身免疫性疾病的免疫调节剂 ,迄今未见火把花根片治疗多发性硬化疗效观察的报导。为探讨火把花根片对 MS的免疫调节机制 ,我们对一组 MS患者应用火把花根片治疗后外周血 T淋巴细胞亚群的变化进行了观察…     

髓鞘碱性蛋白反应性淋巴细胞对神经细胞的作用

目的观察髓鞘碱性蛋白反应性淋巴细胞对人脑神经元细胞及其髓鞘的作用。方法合成髓鞘碱性蛋白83-99肽段,合成肽诱导培养的淋巴细胞与人脑神经细胞共同混合培养,扫描电镜观察。结果髓鞘碱性蛋白反应性淋巴细胞对神经细胞和髓鞘有明显的聚集、黏附和可能的攻击作用,神经细胞的细胞膜和髓鞘有损伤,神经细胞有坏死。结论髓鞘碱性蛋白反应性淋巴细胞对神经细胞和髓鞘有聚集、黏附和可能的攻击作用,可引起髓鞘损伤和神经细胞坏死,这种直接作用可能是多发性硬化症的发病机制之一。     

髓鞘少突胶质细胞糖蛋白抗体在多发性硬化中的意义

目的探讨髓鞘少突胶质细胞糖蛋白(MOG)抗体与多发性硬化(MS)临床表现及复发缓解型MS(RRMS)复发的关系。方法采用酶联免疫吸附法(ELISA)对60例MS、23例其他炎性神经疾病(OIND)、29例非炎性神经疾病(NIND)以及50例神经系统正常的对照(NC)患者血清及脑脊液(CSF)MOG抗体进行检测。结果MS患者CSFMOG抗体阳性率为28.3%(17/60),明显高于NC组[2%(1/50)]和NIND组[0%(0/29)],但与OIND组[21.7%(5/23)]比较差异无统计学意义。各组血清MOG抗体均为阴性。抗体阳性率急性活动期为31.8%(14/44),与稳定期[18.75%(3/16)]比较差异无统计学意义。CSFMOG抗体阳性的RRMS患者复发时间早于阴性患者,且其第1、2年复发率均高于阴性患者。结论在部分MS患者中枢神经系统内存在异常的MOG特异性B细胞免疫应答,且CSFMOG抗体对RRMS的复发有一定预测作用。     

Multislice Brain Myelin Water Fractions at 3T in Multiple Sclerosis

PURPOSE: To evaluate a multislice nonlinearly-spaced 12-echo imaging sequence at 3T covering the supratentorial brain for the quantification of myelin water fraction (MWF) in multiple sclerosis (MS) patients. METHODS: Eighty-nine patients with, or at risk of, MS (69 relapsing remitting MS [RRMS], 7 secondary progressive MS [SPMS], 13 clinically isolated syndrome [CIS]) and 28 controls were studied. Twelve-echo datasets were acquired using a multislice T2 prep spiral imaging sequence and were fitted using a nonnegative least squares algorithm. The mean MWF within normal appearing white matter (NAWM), contrast-enhancing (CE), and nonenhancing T2 lesions were calculated. RESULTS: Mean MWF in white matter for controls was 11.3%. Mean MWF was significantly reduced in NAWM of MS patients (10.6%, P= .004) relative to controls. SPMS/RRMS patients with disease duration >5 years (10.3%) had lower MWF compared to CIS/RRMS with disease duration 相似文献   

多发性硬化与髓鞘抗体及髓鞘碱性蛋白

探讨多发性硬化的免疫发病机制。方法采用ELISA方法测定多发性硬化患者活动期血清（28例）和脑脊液（18例）的GM1抗体、脑磷脂抗体和髓鞘碱性蛋白。结果多发性硬化患者血清GM1抗体阳性率为36％,脑磷脂抗体为43％;脑脊液GM1抗体为11％,脑磷脂抗体为18％,与对照组比较差异均有显著性;血清和脑脊液的髓鞘碱性蛋白增高亦有意义。结论体液免疫参与了多发性硬化的发病过程。可能的机制是,针对自身组织的髓鞘蛋白、髓鞘脂质等自身免疫系统被激活,产生一系列病理改变和临床症状。     

芬戈莫德治疗多发性硬化的中枢神经系统作用机制研究进展

多发性硬化(MS)是一种中枢神经系统广泛脱髓鞘性自身免疫性疾病,至今无特效治疗方法。芬戈莫德(FTY720)是近年研发的一种能有效治疗复发缓解型MS的新型药物。早前认为抑制淋巴细胞迁移可能是其主要作用机制,新近发现芬戈莫德能直接作用于中枢神经系统,并可能是其治疗MS更为重要的机制。文中就芬戈莫德直接作用于中枢神经系统及其相关机制研究进展作一综述。     

多发性硬化患者外周血淋巴细胞Cbl-b的表达

目的分析多发性硬化(MS)患者外周血淋巴细胞Cbl-b基因和蛋白的表达变化并探讨其与MS发病的关系。方法采用RT-PCR和Western-blot方法检测31例MS患者(缓解期20例、急性复发期11例)和16名健康对照者外周血淋巴细胞Cbl-b mRNA和蛋白的表达。结果(1)MS患者外周血淋巴细胞Cbl-b mRNA和蛋白表达水平均较健康对照组明显下调;(2)急性复发期和缓解期MS患者外周血淋巴细胞Cbl-b mRNA表达水平差异无统计学意义;(3)急性复发期MS患者外周血淋巴细胞Cbl-b蛋白表达水平较缓解期患者明显下调。结论外周血淋巴细胞Cbl-b mRNA和蛋白表达下调可能参与了MS发病,且蛋白表达的进一步下调可能与MS急性复发相关。     

Myelin phagocytosis and remyelination of macrophage-enriched central nervous system aggregate cultures.

An increased level of myelin basic protein (MBP) degradation peptide 80-89, representative of myelin breakdown, is detected in myelinating foetal rat brain aggregate cultures supplemented with peritoneal macrophages at a time coinciding with the onset of myelination. During the period of myelination, the proportion of activated macrophages/microglia in the aggregates decreases, accompanied by a reduction in the content of MBP degradation products. During the recovery period following a demyelinating episode, the rate of MBP synthesis in antibody-treated standard aggregates was greater than in their medium controls. However, the rate of MBP accumulation was not as efficient in macrophage-enriched aggregates and was associated with persistently raised MBP peptide levels. Thus, as occurs in multiple sclerosis lesions, attempts at remyelination appear to be counterbalanced by macrophage-mediated demyelination, with the continued presence of degraded myelin rendering a local environment that is not fully conducive to remyelination.     

Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis

Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing–remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs). One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3–2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05–2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05–6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naïve patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01104-8.     

Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination,recognizes an antigen on the surface of oligodendrocytes

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J mice chronically infected with Theiler's virus. To elucidate the mechanism of antibody-mediated remyelination, SCH94.03 was investigated by immunocytochemistry, flow cytometry, immunoelectron microscopy, Western blotting, and immuno-thin layer chromatography. All cell types investigated in vitro showed strong cytoplasmic staining with a pattern resembling a cytoskeletal protein. In contrast, among the primary cultured cells studied, only oligodendrocytes showed strong surface reactivity. Other cell types, including astrocytes, microglia, Schwann cells, myoblasts, and T and B lymphocytes, were negative. Mouse and rat oligodendrocytes which showed strong surface reactivity exhibited a well-differentiated morphology, and ∼50% expressed myelin basic protein. Since oligodendrocyte progenitors were negative for surface staining, the expression of the antigens recognized by this monoclonal antibody appears to be developmentally regulated, i.e., transiently expressed on younger, terminally differentiating oligodendrocytes. Among the cell lines studied, only two rat oligodendrocyte lineage cell lines showed surface reactivity with SCH 94.03. Western blotting of secondary isolated oligodendrocytes lysates revealed reactivity with multiple protein bands of 27, 32, 50, 100, and 106 kDa, whereas there was no reactivity to lipid antigens by immuno-thin layer chromatography. These results raise the possibility that SCH94.03 recognizes a novel oligodendrocyte-specific surface antigen, and may act directly on oligodendrocytes to promote remyelination. © 1996 Wiley-Liss, Inc.