精神分裂症患者自身抗体的研究

为探讨自身免疫与精神分裂症的关系，以便了解精神分裂症发病机制，我们从胎牛脑组织中，以含ＴｒｉｏｎＸ－１００及脱氧胆酸钠的缓冲液提取、亲和层析技术纯化脑细胞膜抗原，建立抗脑抗体ＥＬＩＳＡ法，对９０例精神分裂症患者和６１例健康对照者进行抗脑抗体、抗心磷脂抗体、抗甲状腺球蛋白抗体、抗甲状腺微粒体抗体等自身抗体检测。结果：抗脑抗体阳性率达３７．８％（３４／９０），抗心磷脂抗体３６．７％（３３／９０），抗甲状腺球蛋白抗体达３５．６％（３２／９０），抗甲状腺微粒体抗体达４０％（３６／９０）；与正常对照组比较有显著差异（Ｐ＜０．００１），且女性患者自身抗体阳性率高于男性患者（Ｐ＜０．０５）。提示精神分裂症患者存在免疫功能异常，自身免疫反应可能是其发病的病因之一     

精神分裂症与自身抗体

目的 为探讨精神分裂症与自身抗体的关系。方法 测定了精神分裂症100例61名正常人的血清抗甲状腺球蛋白抗体(TGA)、抗甲状腺微粒体抗体(TMA)、抗心磷脂抗体(ACA),抗脑抗体(ABAb)和抗胰岛素抗体。结果 精神分裂症患者血清中各自身抗体阳性率均偏高;总阳性率为66％,有多种自身抗体者占46％,均明显高于正常人。结论 精神分裂症患者存在着自身免疫倾向;自身抗体在精神分裂症的发病机制中,可能是重要的致病因素。     

精神分裂症与自身抗体关系探讨

为探讨精神分裂症与自身抗体的关系，测定了精神分裂症１００例及正常人６１例血清抗甲状腺球蛋白抗体（ＴＧＡ）、抗甲状腺微粒体抗体（ＴＭＡ）、抗心磷脂抗体（ＡＣＡ）、抗脑抗体（ＡＢＡｂ）和抗胰岛素抗体。结果显示，精神分裂症患者血清各自身抗体阳性率均偏高；总阳性率为６６％，有多种自身抗体者占４６％，均明显高于正常人。研究表明，精神分裂症与自身抗体之间存在内在联系及自身免疫倾向；自身抗体在精神分裂症的发病机制中可能起重要作用。     

系统性红斑狼疮患者免疫功能与自身抗体的关系研究

目的:探讨系统性红斑狼疮(SLE)患者血清免疫功能相关指标(免疫球蛋白IgG、补体C3、补体C4)与自身抗体之间的关系。方法:选取94例SLE患者,81例其他自身免疫系统疾病患者及66例健康对照者分别作为SLE组、非SLE疾病组、健康对照组三组,检测各组血清自身抗体的表达。将SLE组按SLE疾病活动指数(SLEDAI)评分标准分成活动期组和稳定期组,按抗SmD1抗体、抗双链DNA(dsDNA)抗体阴阳性分别分成抗SmD1(+)组、抗SmD1(-)组、抗dsDNA(+)组、抗dsDNA(-)组,与健康对照组一起检测各组血清免疫球蛋白IgG、补体C3、补体C4水平。将以上各组指标进行比较分析。结果:与健康对照组相比,SLE组和非SLE疾病组自身抗体谱中各指标(除Jo-1外)阳性率差异具有统计学意义(P<0.05)。SLE组中抗SmD1抗体、抗dsDNA抗体、抗核小体抗体(AuNA)、抗组蛋白抗体(AHA)、抗核糖体P蛋白(Rib-P)抗体阳性率均比非SLE疾病组高(P<0.05)。SLE活动期组血清免疫球蛋白IgG水平高于SLE稳定期组和健康对照组,而血清补体C3,C4水平低于SLE稳定期组和健康对照组(均P<0.05),SLE稳定期组血清IgG,C3,C4水平和健康对照组相比,血清补体C3,C4水平更低,IgG水平则要高,差异有统计学意义(P<0.05)。SLE组中抗SmD1抗体、抗dsDNA抗体阳性组血清补体C3,C4水平分别低于抗SmD1抗体、抗dsDNA抗体阴性组(均P<0.05)。结论:联合检测免疫球蛋白IgG、补体C3,C4及自身抗体谱可有助于SLE的早期诊断、治疗监测及预后评估。     

脑脊液引流影响颅脑创伤后免疫操作的影响

目的 研究脑脊液引流后创伤大白兔血清中抗脑抗体和IL-1β水平的变化趋势,探讨脑脊液引流对颅脑创伤后免疫损伤的治疗作用。方法 32只大白兔随机分为对照组和脑脊液引流组,每组16只。脑损伤后0-7天取患兔脑脊液1ml,对照组将脑脊液回注入脑池;脑脊液引流组弃去脑脊液。收集第1、3、7、14、21天血清,以ELISA法检测白介素-1β(IL-1β)和抗脑抗体(ABAb)的浓度,并进行对比。结果 脑脊液引流组IL-1β和ABAb浓度较对照组降低（P<0.05）。伤后21天,脑脊液引流组死亡率和致残率较对照组降低,而痊愈率升高。结论 脑脊液引流可以减少脑组织周围的炎性因子,可以减轻颅脑创伤后的免疫损伤。     

丙型肝炎患者血清的自身抗体检测及临床分析

目的：探讨自身免疫反应在丙型肝炎中的作用。方法：应用间接免疫荧光法，以生物薄片马赛克技术制备的冰冻组织细胞切片为抗原与待测血清结合，加入荧光素标记物抗人免疫球蛋白，检测94例丙型肝炎(丙肝)患者血清中抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)、抗肝膜抗体(LMA)和抗肝特异性脂蛋白抗体(LSP)等自身抗体，并根据荧光反映模式判定结果。结果：(1)急性丙肝组患者14例中有6例出现自身抗体阳性，检出率为42．8％；慢性丙肝组80例中自身抗体阳性者30例，检出率37．5％。两组比较差别无统计学意义。(2)抗—HCV阳性的64例中自身抗体阳性者28例，检出率43．75％；HCVRNA阳性的30例中8例抗体阳性，检出率26．67％。结论：HCV感染过程中机体可出现自身免疫反应，HCV患者在常规诊疗过程中应检测自身抗体。     

自身免疫性脑炎患者外周血辅助性T细胞的检测及临床意义

目的分析自身免疫性脑炎患者外周血辅助性T细胞(Tfh细胞)检测的临床意义。方法选取2016年4月-2018年9月云南省曲靖市第一人民医院接诊的血清或脑脊液检测提示自身免疫性脑炎相关抗体阳性患者15例,采集外周血共19例次,并根据患者有无应用免疫抑制剂分成治疗组与未治疗组,根据改良Rankin量表(MRS)评分和临床症状将治疗组患者分成治疗后未缓解组和治疗后缓解组。另选取本院同期接诊的健康体检者14例作为对照组。分离人外周血MBMC,利用四色荧光进行标记,进行FCM分析。选择在冷冻切片大鼠脑组织中培养自身免疫性脑炎相关抗体阳性患者的脑脊液,同时对其施以免疫荧光染色处理,观察其结果。结果未治疗组的外周血Tfh细胞比例高于治疗组和对照组(P均<0.05)。治疗未缓解组的外周血Tfh细胞比例高于治疗缓解组和对照组(P均<0.05)。治疗缓解组的Tfh细胞比例与对照组比较差异无统计学意义(P>0.05)。冷冻切片后,在大鼠脑组织中培养自身免疫性脑炎相关抗体阳性患者的脑脊液,免疫荧光染色显示阳性反应。结论自身免疫性脑炎患者外周血Tfh细胞比例增高与疾病的发生发展有密切关系。     

重症肌无力的治疗进展

重症肌无力(MG)是随意肌的突触后膜乙酰胆碱受体(AchR)的自身免疫性疾病。即由于血中抗AchR抗体对受体的占领、封闭使它不能与乙酰胆碱(Ach)有效地结合;抗体与受体的复合物在补体C3的参与下可溶解受体;杀伤T细胞及淋巴因子并破坏受体;辅助T细胞可促进B细胞合成抗AchR抗体,这种抗体的大部分在胸腺内合成,T淋巴细胞在胸腺内致敏,可引起MG的自身免疫反应的始动抗原(即肌样细胞)也存在于胸腺。现今治疗方式主要是针对抗体、淋巴细胞和胸腺组织的免疫干预治疗以及对症治疗。     

脑脊液中IgG检测方法的建立及临床应用

目的 建立一种稳定的检测脑脊液IgG的方法，为化脓性脑膜炎(化脑)及乙型病毒性脑膜炎(乙脑)的临床诊断和鉴别诊断提供一定的依据。方法 以马抗人IgG抗体作为包被抗体，以酶标兔抗人IgG抗体作为检测抗体建立测定IgG的双抗体夹心ELISA，并对该方法的线性、灵敏度、精密度及回收实验进行评价。同时，用该方法检测了化脑及乙脑患脑脊液标本，并与正常人进行对照。结果 本法测定的IgG浓度在20～320ng／ml范围内呈良好线性关系，灵敏度高，批内和批间平均变异系数(CV)分别为6．8％和7．56％。临床标本检测结果表明正常、化脑及乙脑的脑脊液之间IgG含量均有显性差异。结论 本方法脑脊液IgG测定线性好，重复性好，对临床诊断化脑及乙脑有一定的参考价值。     

小鼠系统性红斑狼疮样综合征的诱导及病变特征

目的 :用ConA活化淋巴细胞的染色质免疫小鼠 ,建立稳定的系统性红斑狼疮 (SLE)样自身免疫反应亢进小鼠模型 ,并进一步观察模型的各项改变。方法 :ConA活化的BALB/c小鼠脾细胞中提取活性染色质。每只以染色质 10 0 μg在d 0 ,14 ,2 8背部皮内注射免疫小鼠 3次 ,建立SLE样自身免疫反应亢进小鼠模型。用ELISA方法测定免疫后血清中抗自身抗体、总IgG的动态生成情况 ;用Hep 2细胞作抗核抗体核型检测。用考马斯亮蓝法测定小鼠尿蛋白含量 ;对小鼠肾脏做病理检查。用硝酸还原酶比色法测定血清一氧化氮 (NO)含量 ,用ELISA方法测定LPS诱导腹腔巨噬细胞产生肿瘤坏死因子 (TNF α)的水平。用 5 0 %溶血试验法测定血清中总补体含量。进行了红细胞、白细胞、血小板计数。结果 :模型小鼠血清抗核抗体 ,总IgG ,NO水平均升高 ,补体下降 ,血象中血小板减少 ,抗核抗体核型为均质型和胞浆型。小鼠有狼疮样肾炎 ,尿蛋白 ,腹腔巨噬细胞TNF α产生减少。结论 :自身活化染色质诱导的SLE样综合征小鼠模型具有与SLE类似病变。     

脑脊液引流对颅脑创伤后免疫损伤的影响

目的:探讨脑脊液引流对颅脑创伤后血清抗脑抗体及白细胞介素(IL)-1β水平的影响.方法:32只大白兔随机分为对照组和脑脊液引流组(引流组),每组16只.脑损伤后0～7 d每天取患兔脑脊液1 mL,对照组将脑脊液回注入脑池;引流组弃去脑脊液.2组均于创伤后第1、3、7、14、21天取血2 mL,分离血清,采用酶联免疫吸附试验(ELI-SA)检测IL-1β和抗脑抗体(ABAb)水平.结果:创伤后对照组ABAb水平逐渐增高,第14天达高峰,之后下降;引流组伤后第1天ABAb水平最高,之后逐渐降低.除第1天外,其他各时点的ABAb水平引流组均低于对照组(P＜0.01).2组创伤后IL-1β水平第1天均最高,之后逐渐降低.除第1天外,其他各时点的IL-1β水平引流组均低于对照组(P＜0.05).引流组好转率高于对照组,病死率低于对照组,差异有统计学意义(P＜0.05).结论:脑脊液引流可以减少脑组织周围的炎性因子,从而减轻颅脑创伤后的免疫损伤.     

Cerebrospinal fluid neuropeptide Y in depression and schizophrenia

Neuropeptide Y (a recently discovered brain peptide that is colocalized with norepinephrine within some adrenergic central nervous system neurons) was measured in the cerebrospinal fluid (CSF) from patients with major affective disorder, chronic schizophrenia, and in normal volunteers. No differences between diagnostic groups were found, suggesting that if this neuropeptide is involved in the pathogenesis of these disorders, an abnormality is not detectable in the CSF.     

In vivo occipital-frontal temperature-gradient in schizophrenia patients and its possible association with psychopathology: a magnetic resonance spectroscopy study

BACKGROUND: Accumulating data suggest that schizophrenia patients' mental status might be modulated by their core/brain temperature. Hence, we intended to assess in vivo brain temperature (Tb) of schizophrenia patients vs. healthy subjects and to evaluate its potential association with patients' mental status. METHODS: Absolute values of Tb were measured in 9 neuroleptic-treated schizophrenia patients and 10 healthy comparison subjects using 1H magnetic resonance spectroscopy (MRS). Values were extracted by measuring the chemical shift between the peaks of water and N-acetyl-aspartate in the 1H MRS spectra. RESULTS: A substantial (about 1.1 degrees C) and significantly higher occipital-frontal temperature-gradient was found in the schizophrenia patients compared to the healthy controls (1.27 degrees C vs. 0.18 degrees C; p=0.032). Furthermore, a trend was found between the above mentioned occipital-frontal temperature-gradient in the schizophrenia patients and the severity of their psychopathology, as assessed by the total Positive and Negative Syndrome Scale (PANSS) scores (r=0.61; p=0.08). CONCLUSIONS: Our findings corroborate previous results indicating putative correlation between core/brain temperature and the mental status of schizophrenia patients, emphasizing the possible role of within patients decreased frontal temperature and a significant occipital-frontal temperature-gradient as modulators of psychopathology. In addition, the MRS technique used for brain temperature assessment seems to be a potential non-invasive method to assess in vivo absolute Tb in schizophrenia.     

Right-hemisphere encephalopathy in elderly subjects with schizophrenia: evidence from neuropsychological and brain imaging studies

Rationale Cognitive impairment is a recognised feature of schizophrenia. Elderly patients with early-acquired schizophrenia are seriously affected, with a proportion of them showing clinically significant dementia, not accounted for by any recognized degenerative processes common in this age group, such as Alzheimer's disease. Progression of cognitive deficits is described in elderly institutionalised patients, but disputed amongst community dwelling subjects. The pattern of cognitive deficits in this age group is not yet clearly defined, although there is some evidence that it differs from that in Alzheimer's disease. There is little evidence of any underlying specific brain abnormality.Objectives To characterize the neuropsychological deficits in elderly schizophrenia patients and distinguish them from those in Alzheimer's disease. To establish the presence of underlying structural brain abnormality using MRI.Methods Twenty-eight elderly schizophrenia patients with onset before the age of 45 years carried out neuropsychology tests. Twelve scored in the dementia range and were compared with 16 equally impaired patients with early Alzheimer's disease. Thirteen of the schizophrenia patients consented to brain MRI. The imaging data were analysed using a newly developed automated method of measuring CSF volume distributions and compared with data from 30 age-matched normal controls.Results The schizophrenia group was more impaired on visuo-spatial tasks than the Alzheimer's group but less impaired on corresponding verbal tasks, despite similar overall cognitive impairment. The MR scans revealed right-sided enlargement of ventral CSF spaces in the schizophrenia patients especially in the posterior third, and this correlated with their impaired performance on visuo-spatial tasks.Conclusions The results suggest that right hemisphere impairment underlies the specific profile of cognitive impairment in elderly patients with schizophrenia.     

The pharmacokinetics of lithium in the brain, cerebrospinal fluid and serum of the rat.

1 Addition of lithium carbonate (55 mmol/kg dry wt.) to the diet of rats for 4 days resulted in ratios between lithium in the brain and serum and between the cerebrospinal fluid (CSF) and serum of approx. 1 and 0.4, respectively. The relationships between the concentrations were linear. 2 After single intraperitoneal injections of lithium chloride (5 mmol/kg body wt.) the concentration of lithium in the CSF was greater than that of the brain for 2 h. 3 Repeated subcutaneous injections of lithium chloride (0.9 mmol/kg body wt.) resulted in steady state ratios corresponding to those observed when lithium was given in the diet. The rate of elimination from the CSF was intermediate between that of the serum and cerebral tissue until a new equilibrium was reached after approx. 24 h. At that time the ratios between lithium in the brain and serum, and in the CSF and serum were increased to approx. 5 and 0.8, respectively. 4 These results are consistent with passive transfer kinetics of lithium in the CSF and elimination of lithium from the cerebral tissue via the CSF. 5 The results may explain some of the phenomena observed in patients during intoxication with lithium.     

Neuropeptides and Alzheimer''s disease

Numerous neuropeptides have been isolated from the human brain and postulated as neurotransmitter candidates. Their biochemical characteristics and anatomical distribution have been elucidated in some detail, but their possible physiological and pathophysiological roles, as well as their utility as diagnostic markers in brain disorders, have been more difficult to establish. The concentrations of several neuropeptides have been measured in postmortem human brain studies and in cerebrospinal fluid (CSF) of patients with Alzheimer's disease. Here we critically review these findings with focus on: (1) the relation between brain tissue and CSF neuropeptide alterations; (2) the specificity of neuropeptide alterations in Alzheimer's disease in relation to other degenerative brain diseases; (3) possible functional implications.     

Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species

Abstract

1. Antiretroviral concentrations in cerebrospinal fluid (CSF) are used as surrogate for brain tissue, although sparse data support this. We quantified antiretrovirals in brain tissue across preclinical models, compared them to CSF, and calculated 90% inhibitory quotients (IQ₉₀) for nonhuman primate (NHP) brain tissue. Spatial distribution of efavirenz was performed by mass-spectrometry imaging (MSI).

2. HIV or RT-SHIV-infected and uninfected animals from two humanized mouse models (hemopoietic-stem cell/RAG2-, n?=?36; bone marrow-liver-thymus/BLT, n?=13) and an NHP model (rhesus macaque, n?=18) were dosed with six antiretrovirals. Brain tissue, CSF (NHPs), and plasma were collected at necropsy. Drug concentrations were measured by LC-MS/MS. Rapid equilibrium dialysis determined protein binding in NHP brain.

3. Brain tissue penetration of most antiretrovirals were >10-fold lower (p?<?0.02) in humanized mice than NHPs. NHP CSF concentrations were >13-fold lower (p?<0.02) than brain tissue with poor agreement except for efavirenz (r?=?0.91, p?=?0.001). Despite 97% brain tissue protein binding, efavirenz achieved IQ₉₀>1 in all animals and 2-fold greater white versus gray matter concentration.

4. Brain tissue penetration varied across animal models for all antiretrovirals except raltegravir, and extrapolating brain tissue concentrations between models should be avoided. With the exception of efavirenz, CSF is not a surrogate for brain tissue concentrations.     

GSK-3 and the neurodevelopmental hypothesis of schizophrenia.

The Neurodevelopmental Hypothesis of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances offer insights into the regulation of brain development. The Wnt family of genes plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3beta (GSK-3beta), accumulation and activation of beta-catenin and expression of genes involved in neuronal development. Alteration in the Wnt transduction cascade, which may represent an aberrant neurodevelopment in schizophrenia, is discussed. Programmed cell death is also an essential component of normal brain development. Abnormal neuronal distribution found in schizophrenic patients' brains may imply aberrant programmed cell death. GSK-3 participates in the signal transduction cascade of apoptosis. The possible role of aberrant GSK-3 in the etiology of schizophrenia is discussed.