癫痫患者血清中抗脑组织抗体的检测

补体结合试验对１１３例癫痫患者及６０例对照血清中抗脑组织抗体（ａｎｔｉ－ｅｎｃｅｐｈａｌｉｃａｎｔｉｂｏｄｙ，ＡＥＡｂ）进行检测，结果：１．癫痫患者ＡＥＡｂ阳性率为４２．２８％，明显高于对照组阳性率８．３３％（Ｐ＜０．０１）。２．原发性癫痫与继发性癫痫之间ＡＥＡｂ阳性率未见差异；ＡＥＡｂ阳性率与年龄、性别、是否用抗痫药亦无明显关系（Ｐ＞０．０５）。３．ＡＥＡｂ阳性率与癫痫病程长短有关（Ｐ＜０．０５）；与脑电图是否异常、用药效果、发作类型有关（Ｐ＜０．０１）     

人类白细胞抗原配型及其抗体监测在亲属活体供肾移植中的应用

背景：人类白细胞抗原(HLA)配型是影响肾移植效果的重要因素，其抗体检测有助于筛查术前致敏者。 目的：探讨人类白细胞抗原配型联合抗人类白细胞抗原抗体监测在亲属活体供肾移植中的应用价值。 设计、时间及地点：单一样本观察，病例回顾性分析，于2004-02/2007-09在中山大学附属第一医院完成。 对象：选择同期中山大学附属第一医院行亲属活体供肾者、首次肾移植者66例，供者男27例，女39例，年龄19~66岁；受者男50例，女16例。 方法：采用序列特异性引物聚合酶链反应法测定拟行亲属活体肾移植的供、受者人类白细胞抗原A，B，DR抗原分型，采用补体依赖微量细胞毒性试验于术前行交叉配型。采用甲泼尼龙联合抗CD25单克隆抗体或抗胸腺细胞球蛋白于术中和术后早期作免疫诱导治疗，采用以环孢素A或他克莫司为主联合吗替麦考酚酯和泼尼松的三联方案作维持性免疫抑制治疗。 主要观察指标：采用酶联免疫吸附法筛查和监测受体的群体反应性抗体；检测肾移植效果及不同免疫抑制方案患者急性排斥情况。 结果：66例亲属活体供肾移植中，供受者人类白细胞抗原A，B，DR配型错配数分别为0~3个60例，4~6个6例。在0~3 错配数受体中，术后3例(5%)发生移植肾功能延迟恢复，4例(7%)发生急性排斥。在4~6错配数受体中，术后1例(17%)移植肾功能延迟恢复、2例(33%)急性排斥。人类白细胞抗原0~3 错配数和4~6 错配数两组比较，其移植肾功能延迟恢复和急性排斥发生率差异均有显著性意义(P < 0.05)。不同免疫抑制治疗方案对移植肾功能延迟恢复和急性排斥发生率无显著影响(P > 0.05)。所有急性排斥患者经甲泼尼龙和/或抗胸腺细胞球蛋白等治疗后逆转。对3例术前预致敏受者术后定期监测群体反应性抗体变化：1例群体反应性抗体水平无明显变化，移植肾功能顺利恢复；2例术前经血浆置换后转阴或自然转阴，术后发生急性排斥，经甲泼尼龙、抗胸腺细胞球蛋白等治疗后逆转。 结论：亲属活体供肾组织配型中，人类白细胞抗原配型与肾移植术后急性排斥、移植肾功能延迟恢复等相关。术前组织配型及抗人类白细胞抗原抗体动态监测对于亲属活体供肾移植特别是预致敏受者很重要。     

同时测定血清猪囊虫特异性抗体及循环抗原的临床价值

检测１４０例癫痫病人血清猪囊虫抗体。并对３０例抗体阳性者进行循环抗原（ＣＡｇ）测定。结果；抗体阳性为５８例（４１％），ＣＡｇ阳性１２例（４０％）。经脑ＣＴ证实１２例抗体及ＣＡｇ阳性者均为活动性病变。表明，同时测定抗体和ＣＡｇ可作为诊断活动其脑囊虫可靠方法。     

90例精神疾病患者血清抗脑抗体测定

对住院精神疾病患者进行血清抗脑抗体测定。1　对象和方法为我院住院精神疾病患者。共 90例 ,男 6 9例 ,女 2 1例。年龄 11～ 88岁。应用酶联免疫吸附法 (ELISA)测定患者血清中抗脑抗体(ABAb)水平。试剂盒由上海玉兰生物技术研究所提供。用雷杜RT 2 10 0酶标仪读反应结果的吸光度值。在 10分钟内出现明显兰色者为阳性 ,无色、浅兰色为阴性。酶标仪测定时用 2MH2 SO4终止反应 ,在 4 5 0nm波长下比色 ,结合肉眼观察结果。OD值≥ 0 35者为阳性。2　结果90例中 2 7例血清抗脑抗体阳性 ,阳性率 30 %。阳性标本平均OD值为 0 4 6± 0 11…     

神经系统疾病患者血清中抗脑抗体的检测

测定235例7种神经系统疾病患者血清中抗脑抗体,发现癫痫组、脑血管病组、重症肌无力组、小脑型共济失调组的阳性率高于对照组,差异有极显著性意义(P<0.01);并且癫痫组,脑血管病组,重症肌无力组病人血清中抗脑抗体的平均滴度高于对照组,差异有极显著性意义(P<0.01)     

实验性自身免疫性脑脊髓炎小鼠脑内主要组织相容性复合体Ⅱ类抗原和分化群3ε的变化

目的观察实验性自身免疫性脑脊髓炎(EAE)小鼠脑内主要组织相容性复合体Ⅱ类抗原(MHC-Ⅱ)和分化群3ε(CD3ε)的变化。方法 25只C57BL/6小鼠随机分为EAE组(n=13)和正常对照组(n=12)。应用髓鞘少突胶质细胞糖蛋白35-55抗原诱导小鼠EAE模型。观察记录小鼠行为学变化;采用常规及髓鞘染色方法观察脊髓损伤和炎症细胞浸润程度;荧光定量PCR检测脑MHC-Ⅱ和CD3εmRNA的表达。结果 EAE组小鼠发病后EAE症状评分逐渐增加;脊髓炎症细胞浸润明显;髓鞘脱失较多;脑组织MHC-Ⅱ和CD3εmRNA表达显著高于正常对照组(均P<0.01),并与EAE症状评分呈正相关。结论 EAE小鼠脑内MHC-Ⅱ及CD3εmRNA表达水平增高与其病情严重程度一致。     

同时测定血清猪囊虫特异性抗体及循环抗原的临床价值

检测１４０例癫痫病人血清猪囊虫抗体，并对３０例抗体阳性者进行循环抗原（ＣＡｇ）测定。结果：抗体阳性为５８例（４１％），ＣＡｇ阳性１２例（４０％）。经脑ＣＴ证实１２例抗体及ＣＡｇ阳性者均为活动性病变。表明，同时测定抗体和ＣＡｇ可作为诊断活动期脑囊虫病的可靠方法。     

抗谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体与难治性癫痫的相关性研究

目的探讨抗谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体与成人难治性癫痫发病机制的相关性。方法本研究分为3组,即正常对照组(NC组)、可控性癫痫组(NE组)以及难治性癫痫组(IE组)各30例,其中NC组来自医院体检中心的健康体检人员;NE组及IE组来自吉林大学第一医院神经内科癫痫诊疗中心。以酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测3组的血清抗谷氨酸脱羧酶抗体、抗心磷脂抗体及抗神经节苷脂抗体数值,采用正态性检验,两组间定量资料比较。结果 IE组的血清3种抗体水平显著高于NE组及NC组,NE组和NC组的抗体浓度比较无统计学意义;3种抗体检测对于难治性癫痫的诊断具有高度一致性。结论成人难治性癫痫中谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体的检测对于难治性癫痫的诊断、治疗及预后判断具有指导作用。     

神经、精神疾病的抗脑抗体研究进展

神经-内分泌-免疫三大系统组成了机体最大、最复杂的调控网络。近年来,由于神经免疫学的进一步发展,有关中枢神经系统疾病后抗脑抗体变化及对机体影响的研究逐渐增多,涉及神经退行性疾病、脑出血、癫痫、精神疾病、感染免疫疾病、慢性酒精中毒、颅脑肿瘤、颅脑创伤等。抗脑抗体是由免疫系统产生的针对脑组织抗原的自身抗体,抗脑抗体包括针对脑组织S100蛋白、神经元特异性烯醇化酶、髓磷脂碱蛋白等的自身抗体。现就相关研究进展综述如下。     

94例缺血性脑卒中患者HLA基因表达分析

目的 探讨人类白细胞抗原(HLA)基因遗传与缺血性脑卒中发病的关联.方法 采用聚合酶链反应-直接测序分型技术(PCR-SBT)对广东医学院附属南山医院2008年收治的94例缺血性脑卒中患者和同期122例正常对照者进行HLA-A、B、DRB1位点的等位基因分型.结果 缺血性脑卒中患者表达HLA-A位点16个等位基因,HLA-B位点32个等位基因,HLA-DRB1位点25个等位基因.患者组HLA-A*1102基因频率较对照组明显降低,HLA-A*1102与缺血性脑卒中呈负相关(RR=0.06,P=0.019).结论 JLA-A*1102与缺血性脑卒中呈易感负相关,提示HLA等位基因与缺血性脑卒中的发生存在遗传免疫关联,对该病具有临床预测意义.

Abstract：

Objective To discuss the relationship between human leukocyte antigen (HLA) gene heredity and morbidity of cerebral infarction by a random survey on the allele expression of HLA-A, B and DRB1 seats of patients with cerebral infarction. Methods The genotypes of HLA-A, B and DRB1 alleles in 94 patients with cerebral infarction and 122 healthy blood donors were detected by polymerase chain reaction-sequencing based typing (PCR-SBT) method. Results Sixteen alleles in HLA -A locus,32 alleles in HLA -B locus and 25 alleles in HLA -DRB1 locus expressed themselves in these patients with cerebral infarction. The gene frequency of HLA -A*1102 in patients was lower than that in healthy controls, and negative association was found between HLA -A* 1102 allele and cerebral infarction (RR=0.06,P=0.019). Conclusion The research reveals susceptibility association of HLA -A*1102 with patients having cerebral infarction, displaying close genetic immunity correlation between HLA alleles and pathogenesis of cerebral infarction. So, the research in this paper is useful in the clinical prediction of this disease.     

Human leukocyte antigen alleles in patients with bipolar disorder in the Korean population

We performed an association study between human leukocyte antigen (HLA) alleles and bipolar disorder to evaluate the potentiality of HLA as a genetic marker in bipolar disorder. HLA class I and class II allele frequencies were assessed in 87 bipolar patients and were compared with those of 206 normal controls in the Korean population. HLA class I typing was performed using the microlymphocytotoxicity method, whereas class II (DRB1 and DQB1) genotyping was performed with polymerase chain reaction-sequence specific oligonucleotide probes. When the allele frequency of HLA in bipolar patients was compared with that in normal controls, there were some significant differences. Bipolar patients showed statistically significant increased allele frequencies of HLA-A29 and B54. Allele frequencies of HLA-B51 and DRB1*02 were significantly higher in normal controls. However, these results were no longer significant after correcting for the number of alleles. The results of the present study suggest that HLA alleles may not confer susceptibility to bipolar disorder in the Korean population. To clarify the genetic influence of HLA on bipolar disorder, we should conduct a consecutive study with a larger cohort of subjects.     

Human leukocyte antigen class I in polymyositis: Leukocyte infiltrates,regeneration, and impulse block

In polymyositis (PM), T-cell mediated myocytotoxicity is directed against strongly human leukocyte antigen class I positive (HLA-I⁺) muscle fibers. Fiber regeneration probably is partly responsible for this HLA-I up-regulation. We have evaluated regeneration, denervation/impulse blockade, and focal leukocyte infiltrates as possible HLA-I inducing factors in PM. Distinctive patterns of HLA-I, nerve cell adhesion molecule (NCAM), and vimentin expression accompany denervation and regeneration. Regenerating fibers also have centralized nuclei. Using semiquantitative methods, we examined strongly HLA-I⁺ fibers in PM muscle biopsies for these markers. Sarcoplasmic HLA-I levels were related to the presence of leukocyte infiltrates and invasion of fibers. Strongly HLA-I⁺ fibers were frequently invaded, and regeneration-associated changes were usually observed at sites of fiber damage. Sarcoplasmic HLA-I levels were stable along intact fibers, also adjacent to leukocyte infiltrates. A majority of the strongly HLA-I⁺ fibers were nonregenerating (NCAM⁺ only). Though other mechanisms cannot be excluded, this suggests that impulse blockade or denervation may contribute to extra HLA-I up-regulation in these fibers. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1534–1540, 1997     

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

Purpose: Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined. Methods: We analyzed GADA with a radioimmunoassay in sera of 253 well‐characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies. Results: GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [≥1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA‐positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra‐TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39–4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001). Discussion: High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.     

Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.     

Serum Fas and Bcl-2 in patients with epilepsy

OBJECTIVES: The present study aimed to investigate the levels of the biochemical markers of apoptosis (soluble Fas and Bcl-2) in the sera of children and adolescents with idiopathic epilepsy. MATERIALS AND METHODS: The study included 30 children and adolescents (mean age 8.03 +/- 4.49 years) with idiopathic epilepsy, 16 of them were newly diagnosed, and 15 clinically healthy control subjects. Of the included patients, 22 had focal seizures and eight had generalized seizures. In addition to laboratory and radiological investigations needed for diagnosis and follow-up, soluble Fas (s.Fas) and Bcl-2 were assayed in sera of patients and controls by enzyme-linked immunosorbent assay technique. RESULTS: Serum levels of s.Fas and Bcl-2 were significantly higher in the patients group than in the control group; however, their levels were comparable in patients with different seizure types. Levels of s.Fas correlated positively with seizure severity and negatively with the duration from the last attack. Bcl-2 levels were positively correlated to each of the duration of epilepsy, the severity of seizures and its frequency. There was a significant positive correlation between serum levels of s.Fas and that of Bcl-2 and both were significantly increased in patients with uncontrolled epilepsy. CONCLUSION: The present data demonstrate that markers of apoptosis, both the proapoptotic Fas and the anti-apoptotic Bcl-2, were proportionately elevated in sera of patients with idiopathic epilepsy, and their levels were related to the seizure severity and frequency.     

Higher expression of monocyte chemoattractant protein 1 and its receptor in brain tissue of intractable epilepsy patients

We aimed to explore the pathogenesis of monocyte chemoattractant protein-1 (MCP1) and CC chemokine receptor 2 (CCR2) in brain tissue of patients with intractable epilepsy (IE). Hippocampi or temporal lobe tissues were obtained from 40 patients with IE and five patients without IE who had undergone surgical decompression and debridement. The levels of MCP1 and CCR2 were evaluated using immunohistochemistry. Pearson correlation analysis was employed to evaluate the correlation between levels of MCP1 and CCR2 in IE with or without hippocampal sclerosis (HS) and the disease duration, along with age. Higher levels of MCP1 (11.68 ± 4.68% versus 1.72 ± 1.54%) and CCR2 (11.54 ± 4.65% versus 1.52 ± 1.29%; P < 0.05) were observed in IE patients compared to controls. Expression levels of MCP1 (R = 0.867) and CCR2 (R = 0.835) in IE patients with HS were correlated with the disease duration. However, no correlation was found in IE patients without HS. There was also no correlation between levels of MCP1 and CCR2 in IE patients with age, either with HS or without HS. These results suggest that MCP1 and its receptor may play a role in the pathogenesis and progression of IE.     

Immunohistochemical staining of human brain with monoclonal antibodies that identify lymphocytes, monocytes, and the Ia antigen

Using immunoperoxidase histochemistry, human brain sections obtained at biopsy were labeled with monoclonal antibodies which identify human lymphocytes subsets, monocytes, and the Ia antigen. Staining of a population of cells in white matter was present with the anti-Ia and the anti-M1 (monocyte-associated) antibodies but not with any of the 8 monoclonal antibodies which react with human T-cell subsets (anti-T1, 3, 4, 5, 6, 8, 10 and 12). The Ia antigen was present on 1–2% of cells in white matter, and approximately 5% of cells in white matter were M1-positive. Ia-positive cells demonstrated a pattern of diffuse surface membrane staining whereas the M1 antigen appeared to cluster at proximal cell processes. Definitive identification of these cells as microglial cells, astrocytes or oligodendrocytes was not possible.These findings demonstrate that: (1) cells which beam the Ia and M1 determinants can be found in histologically normal human white matter, and (2) human oligodendrocytes do not react with monoclonal antibodies (anti-T5 and anti-T8) that identify human suppressor/cytotoxic cells.