急性脑梗死和Alzheimer病脑脊液高水平髓鞘素抗原B细胞免疫应答

目的确认急性脑梗死（ＡＣＩ）和Ａｌｚｈｅｉｍｅｒ病（ＡＤ）对髓鞘素碱性蛋白（ＭＢＰ）、髓鞘素结合糖蛋白（ＭＡＧ）和含脂质蛋白（ＰＬＰ）的Ｂ细胞免疫应答。方法采用酶联免疫斑点技术检测了ＡＣＩ、临床可能ＡＤ和其它神经疾病（ＯＮＤ）对照组患者外周血和脑脊液（ＣＳＦ）中ＭＢＰ、ＭＡＧ和ＰＬＰ抗体分泌细胞。结果ＡＣＩ、ＡＤ和ＯＮＤ患者外周血中均可检出ＩｇＧ、ＩｇＡ、ＩｇＭ三种表型ＭＢＰ、ＭＡＧ、ＰＬＰ抗体分泌细胞，无显著差异。但ＡＣＩ和ＡＤ患者ＣＳＦ中ＩｇＧ型ＭＢＰ、ＭＡＧ和ＰＬＰ抗体分泌细胞均呈显著性增高。结论ＡＣＩ急性脑缺血损伤和ＡＤ神经变性可能导致体内Ｂ细胞激活及ＣＮＳ内髓鞘素反应性Ｂ细胞免疫应答，其病理意义有待探讨。     

急性脑梗死和Alzheimer病脑脊液高水平髓鞘素抗原B细胞免 …

目的 确认急性脑梗死对髓鞘素碱性蛋白（ＭＢＰ）,髓鞘素结合糖蛋白（ＭＡＧ）和含脂质蛋白（ＰＬＰ）的Ｂ细胞免疫应答。方法 采用酶联免疫斑点技术检测了ＡＣＩ,临床可能ＡＤ和其它神经疾病（ＯＮＤ）对照组患者外周血和脑脊液（ＣＳＦ）中ＭＢＰ,ＭＡＧ和ＰＬＰ抗体分泌细胞。     

Alzheimer型痴呆的髓鞘素蛋白自身应答性T细胞免疫反应

通过计数分泌细胞因子γ－干扰素（ＩＦＮ－γ）、辅助性Ｔ细胞（Ｔｈ１），检查ＡＤ患者外周血和脑脊液（ＣＳＦ）中Ｔ细胞免疫应答。方法：将单个核细胞（ＭＮＣ）暴露于中枢神经系统（ＣＮＳ）髓鞘素抗原髓鞘碱性蛋白（ＭＢＰ）和含脂质蛋白（ＰＬＰ）中进行体外短时间培养，用酶联免疫斑点试验（Ｅｌｉｓｐｏｔ）检测ＩＦＮ－γ分泌性Ｔｈ１细胞链，同时检测急性脑血管病（ＣＶＤ）和其他神经疾病（ＯＮＤ）患者作为对照。结果显示ＡＤ患者外周血中呈高水平ＭＢＰ应答性Ｔｈ１细胞链，而其ＣＳＦ中尤为明显，外周血中ＰＬＰ应答性Ｔｈ１细胞亦显著高于ＯＮＤ对照组。结论认为ＡＤ患者存在高水平的髓鞘素蛋白自身应答性Ｔ细胞反应，且在与ＣＮＳ紧邻的ＣＳＦ中表现得尤为显著，其在ＡＤ发病机制中的作用还有待进一步深入探讨。     

急性脑梗塞患者分泌γ—干扰素的特异性髓鞘素记忆性T细胞的研究

通过计数分泌细胞因子γ－干扰素记忆性Ｔ细胞，观察急性脑梗塞（ＡＣＩ）患者的特异性Ｔ细胞免疫应答。方法采用酶联免疫斑点法（ＥＬＩＳＡ）检测了３２例ＡＣＩ、２４例炎症性神经疾病（ＯＩＮＤ）和２５例其他神经疾病（ＯＮＤ）患者髓鞘素抗原及其多肽应答性Ｔ细胞。结果ＡＣＩ患者外周血髓鞘素碱性蛋白（ＭＢＰ）及其多肽和含脂质蛋白（ＰＬＰ）自身抗原应答性Ｔ细胞数呈显著增高，脑脊液（ＣＳＦ）中ＭＢＰ应答性Ｔ细胞数约为外周血中的１１０倍。结论这种免疫应答可能是继发于急性缺血后的脑组织损伤，且在紧邻靶器官的ＣＳＦ中表现尤为明显，其病理意义还有待进一步探讨。     

脑脊液髓鞘碱性蛋白抗体检测对格林—巴利综合 …

目的 探讨格林－巴利综合征（ＧＢＳ）中枢神经髓鞘的免疫性损伤，方法ＧＢＳ患者２０例，神经系统其它疾病组（ＯＮＤ）２０例，非神经系统疾病手术者３３例，以酶联免疫吸附法检测了７３份脑脊液（ＣＳＦ）中髓鞘碱性蛋白ＩｇＧ（ＭＢＰ－ＩｇＧ）。结果 ＧＢＳ患者，ＯＮＤ患者和非神经系统疾病手术者ＣＳＦ中ＭＢＰ－ＩｇＧ阳性经分别为５５％，３０％和９．１％，ＧＢＳ患者ＣＳＦ中ＭＢＰ－ＩｇＧ阳性率与发病天线有关，结论     

急性闭合性颅脑损伤患者血清髓鞘碱性蛋白及其抗体含量的…

用酶联免疫吸附法（ＥＬＩＳＡ）测定３６例急性闭合性颅脑损伤（ＡＣＨＴ）患者、４０例其它神经系统疾病（ＯＮＤ）患者及３２名正常人的血清髓鞘碱性蛋白（ＭＢＰ）及其抗体（Ａｎｔｉ－ＭＢＰ）含量。结果表明：ＡＣＨＴ组患者血清ＭＢＰ含量显著高于ＯＮＤ组与正常人组（均Ｐ〈０．０１），ＡＣＨＴ患者中脑挫裂伤组和脑内血肿组血清ＭＢＰ含量较脑震荡组明显增高（均Ｐ〈０．０１）；而ＯＮＤ组与正常人组比较则无明显差异（Ｐ     

髓鞘碱蛋白对脑梗死和多发性硬化的诊断价值

目的探讨髓鞘碱蛋白（ＭＢＰ）对脑梗死（ＣＩ）和多发性硬化（ＭＳ）的诊断价值。方法对１１４例ＣＩ患者、２８例ＭＳ患者、２４名正常者血清以及部分患者脑脊液（ＣＳＦ）的ＭＢＰ进行了检测。结果ＣＩ、ＭＳ患者血清和ＣＳＦ的ＭＢＰ均显著高于正常对照组（Ｐ〈０．０１）,ＭＳ组又高于ＣＩ组（Ｐ〈０．０１）;ＭＳ组中病情活动期患者ＭＢＰ又高于缓解期。结论血清和ＣＳＦ的ＭＢＰ检测对ＭＳ和ＣＩ的鉴别诊断,以及判断ＭＳ病     

急性闭合性颅脑损伤患者血清髓鞘碱性蛋白及其抗体含量的研究

用酶联免疫吸附法（ＥＬＩＳＡ）测定３６例急性闭合性颅脑损伤（ＡＣＨＴ）患者、４０例其它神经系统疾病（ＯＮＤ）患者及３２名正常人的血清髓鞘碱性蛋白（ＭＢＰ）及其抗体（Ａｎｔｉ－ＭＢＰ）含量。结果表明：ＡＣＨＴ组患者血清ＭＢＰ含量显著高于ＯＮＤ组与正常人组（均Ｐ＜０．０１），ＡＣＨＴ患者中脑挫裂伤组和脑内血肿组血清ＭＢＰ含量较脑震荡组明显增高（均Ｐ＜０．０１）；而ＯＮＤ组与正常人组比较则无明显差异（Ｐ＞０．０５）。ＡＣＨＴ组患者血清Ａｎｔｉ－ＭＢＰ含量与ＯＮＤ组比较差别无显著性（Ｐ＞０．０５）。提示血清ＭＢＰ含量对判断颅脑损伤的病情有重要价值。     

重型颅脑损伤患者血清和脑脊液髓鞘碱性蛋白变？…

目的 探讨颅脑损伤患者血清和脑脊液（ＣＳＦ）中髓鞘碱性蛋白（ＭＢＰ）含量变化。方法 采用酶联免疫吸附法测定了６０例重型颅脑损伤患者的血清和ＣＳＦ中ＭＢＰ含量。结果 患者血清和ＣＳＦ中ＭＢＰ含量均增高,其上升水平与脑损伤类型及程度有关。结论同步检测血清和ＣＳＦ中ＭＢＰ含量变化,对判断颅脑损伤的程度及类型有一定实用价值。     

AChRAb阳性和阴性重症肌无力患者IL—4和IFN—γ…

将行胸腺切除术的重症肌无力（ＭＧ）患者分成乙酰胆碱受体抗体（ＡＣｈＲＡｂ）阳性和阴性２组，采用免疫酶点法检测其外周血、骨髓和胸腺白细胞介素４－（ＩＬ－４）分泌细胞和干扰素－γ（ＩＦＮ－γ）分泌细胞的数量，结果表明ＡＣｈＲＡｂ阳性组其外周血和骨髓中ＩＬ－４和ＩＦＮ－γ分泌细胞数量均显著高于ＡＣｈＲＡｂ阴性组（Ｐ〈０．０５），而胸腺细胞两组间差异无显著性意义（Ｐ〉０．０５）。提示ＩＬ－４和ＩＦＮ－γ在     

亚低温治疗对实验性脑出血大鼠死亡率及脑组织钙含量的影响

目的本研究观察３２℃亚低温对实验性脑出血大鼠２４ｈ内死亡率和脑组织钙含量的影响。方法１３４只大鼠分成两部分：（１）６８只大鼠用于死亡率观察;（２）６６只大鼠用于脑组织钙含量测定。每一部分分成假手术对照组、常温脑出血组及亚低温脑出血组。结果常温组２４ｈ内死亡率为３６．６７％,亚低温组为４．５５％;脑组织钙含量常温组较对照组和亚低温组为高。结论亚低温治疗能显著减少实验性脑出血大鼠２４ｈ内死亡率,减少脑出血后脑组织钙含量。     

Persistent anti-myelin basic protein IgG antibody response in multiple sclerosis cerebrospinal fluid

Antibodies to myelin components, such as myelin basic protein (MBP), may play a role in pathogenesis of multiple sclerosis (MS) but results from determinations of anti-MBP antibodies are inconsistent. Enumeration of cells secreting antibodies represents a new approach to evaluate a specific antibody response regarding extent and localization, and reduces effects of e.g. antibody binding to target. Anti-MBP IgG antibody secreting cells were present in MS patients' cerebrospinal fluid (CSF) at a mean value of 1 per 833 cells, and they amounted to a mean value of about 2454 in the whole CSF compartment. Similar numbers were encountered in patients with other inflammatory neurological diseases (OIND). During follow-up, anti-MBP IgG antibody secreting cells persisted regarding frequency and numbers in MS, but decreased in OIND. Such cells were rarely detected in patients with tension headache. No correlations to clinical exacerbation of MS, disability or duration were discernable. In blood from MS and OIND patients, anti-MBP IgG antibody secreting cells were detected infrequently and at low numbers. The anti-MBP antibody response is strongly restricted to the IgG isotype. The anti-MBP IgG antibody response which is persistent and compartmentalized to the diseased organ, may be important for the development of MS.     

Immunoglobulin producing cells in bone marrow and blood of patients with multiple sclerosis and controls.

Multiple sclerosis (MS) is characterised by intrathecal synthesis of IgG, less frequently of IgA and IgM. Local production of antibodies to myelin basic protein (MBP) and other myelin components has also been reported, and autoimmune pathogenesis has been postulated. Whether MS is accompanied by a systemic B cell response is less clear. To elucidate this question, we examined bone marrow and peripheral blood from patients with MS and controls for cells secreting IgG, IgA and IgM, as well as anti-MBP antibodies of these three isotypes. Patients with MS without any signs of concurrent infections had higher numbers of IgG + IgA + IgM secreting cells both in bone marrow and peripheral blood compared with healthy controls. The same abnormalities were observed in patients with other inflammatory neurological diseases (OIND). When analysing individual isotypes, patients with MS and OIND had higher numbers of IgA secreting cells both in bone marrow and blood compared with healthy controls. Only one of 13 MS patients examined had anti-MBP antibody secreting cells in bone marrow and blood. The systemic B cell response registered in MS is also present in other inflammatory neurological diseases and its specificity and possible role in the pathogenesis of MS remains unknown.     

Immunoglobulin-producing cells in CSF and blood from patients with multiple sclerosis and other inflammatory neurological diseases enumerated by Protein-A plaque assay

Using the Protein-A plaque assay, numbers of IgG + IgA + IgM producing cells determined in patients with multiple sclerosis (MS) were 0.1–5% in CSF and 0.1–0.7% in peripheral blood; interestingly, 7 of 11 MS patients had IgM producing cells in CSF. In patients with aseptic meningitis (AM), the corresponding values were 0.04–7.5% in CSF and 0.4–2.4% in peripheral blood. There were more Ig producing cells in peripheral blood from patients with AM and MS than in healthy subjects. cocorrelation between numbers of IgG producing cells in CSF and the concentrations of intrathecally produced IgG (CSF IgG index) was registered in patients with AM: the same was true for IgA. The Protein-A plaque method, adopted for 20 × 10³ lymphocytes, makes possible enumeration of Ig-producing cells in CSF and discrimination among cells secreting different Ig classes, thereby being a powerful tool for studying immune reactions in the CNS-CSF compartment.     

Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis.

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.     

Virus-reactive and autoreactive T cells are accumulated in cerebrospinal fluid in multiple sclerosis

Elevated numbers of B cells--plasma cells secreting antibodies to measles and mumps virus, and to myelin associated glycoprotein (MAG), one of several putative myelin autoantigens--have previously been reported in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), while it is unknown if corresponding T cell reactivities occur. We have defined the T cell reactivities to measles and mumps virus and to MAG in an immunospot assay which is based on the detection of secretion of interferon-gamma (IFN-gamma) by single cells upon stimulation with specific antigen in short term cultures. Patients with MS had higher numbers of MAG-reactive T cells in blood compared to controls, while no differences were observed for measles or mumps virus-reactive T cells. In CSF, elevated numbers of MAG-reactive T cells and also of measles- and mumps-reactive T cells were found in patients with MS compared to other neurological diseases. A strong accumulation of antigen-reactive T cells was observed in the MS patients' CSF compared to blood. The magnitude of these T cell reactivities did not correlate with clinical MS variables. The T cell repertoire in MS thus includes, besides myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein, also MAG and, in addition, measles and mumps virus. It is not clear whether these T cell reactivities accumulated in the CSF have importance for the pathogenesis of MS or reflect phenomena secondary to myelin damage, or result from both these alternatives.     

Distribution of plasma cells secreting antibodies against nervous tissue antigens during experimental allergic encephalomyelitis enumerated by a nitrocellulose immunospot assay

The B cell response to central nervous system (CNS) myelin and myelin basic protein, as well as total numbers of IgG secreting cells, was studied in acute experimental allergic encephalomyelitis using a nitrocellulose immunospot assay. The method was able to detect single plasma cells secreting antibodies. Cells secreting antibodies against myelin antigens were detected in regional lymph node cell suspension by day 5 post-immunization (p.i.). At that time no anti-myelin antibodies were detected free in serum. Later, at day 15 p.i., specific antibody secreting cells were found in bone marrow and spleen indicating a generalization of the immune response. The B cell response became partly sequestered to the target of immune attack since an increased number of IgG secreting cells was detected among mononuclear cells recovered from the CNS. Studies of cellular secretion of antibodies rather than free levels in body fluids may be a more accurate reflection of the in vivo B cell response. These findings may be generally considered in studies of B cell mediated immunity in neuroinflammatory diseases.     

Estradiol potentiates poke-weed mitogen-induced B cell stimulation in multiple sclerosis and healthy subjects

Female preponderance in many diseases suggested with autoimmune pathogenesis, multiple sclerosis (MS) being classified as one of them, indicates a role for hormonal factors such as estrogen in disease development. To bypass monthly hormonal fluctuations in females, we evaluated in male patients with MS and male blood donors the effect of 17-beta-estradiol on numbers of IgG, IgA and IgM producing cells in cultures of peripheral blood lymphocytes. While estradiol alone had no effect, estradiol in combination with poke-weed mitogen (PWM) yielded in both groups higher numbers of IgG and IgA producing cells when compared with numbers obtained by PWM stimulation alone, indicating an additory effect of estradiol to that of PWM on B cell maturation. This effect was less pronounced in MS than in blood donors, especially for IgG producing cells, probably reflecting higher B cell activation in vivo taking place in MS. On the contrary, cells producing IgG, IgA and IgM antibodies against myelin, myelin basic protein and measles virus were not detectable after stimulation with PWM, nor with PWM and estradiol. Estradiol can in many patients with MS and in blood donors be considered a potent co-activator of B cells in presence of B cell stimulating factor in the form of PWM.     

Myelin basic protein antibodies in the serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients

A solid-phase radioimmunoassay was developed for the detection of myelin basic protein antibodies of immunoglobulin G (IgG) class. Purified basic protein of myelin (MBP) was adsorbed onto polystyrene beads, followed by incubation in dilutions of serum or cerebrospinal fluid (CSF). ¹²⁵I-labelled anti-human IgG was used to quantify antibodies bound to the solid-phase. The assay was optimized in tests with rabbit antibodies to MBP and with ¹²⁵I-labelled anti-rabbit IgG.
Serum and CSF specimens from 41 multiple sclerosis (MS), 16 subacute sclerosing panencephalitis (SSPE) and 58 control patients were tested for MBP antibodies. No statistically significant differences were found between MS and control patient groups, but the subgroup of acute MS patients had slightly elevated ( P 0.02) antibody levels in their CSF specimens. The SSPE patients had markedly elevated levels ( P 0.001) of antibodies to MBP in their CSF specimens.     

Binding properties of cerebrospinal fluid IgG in multiple sclerosis and other neurological diseases

A solid phase radioimmunoassay (RIA) was used to detect antibodies to myelin or myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or other neurological diseases (OND). When measured at the same IgG concentration, MS samples had higher binding values than OND against myelin, but not against MBP. Using F(ab')2 fragments purified from pools of MS and OND CSF there was no difference in binding to myelin between MS and OND samples. These results indicate that anti-MBP antibodies are nt a feature of MS and binding of CSF IgG to myelin is not due to specific antibody, but is probably the result of non-specific binding to Fc receptors.