副肿瘤综合征抗Hu抗体对培养神经细胞的直接影响

目的研究副肿瘤综合征(PNS)自身抗体(抗Hu抗体)对培养神经细胞的直接影响。方法抗Hu抗体阳性PNS患者血清IgG、对照组血清IgG添加到由胎鼠脑分离出的培养神经细胞,观察有无细胞的凋亡。对照组血清IgG为：(1)AB型健康人标准血清；(2)无神经损害症状的抗Hu抗体阴性痛患者血清；(3)重组Hu蛋白吸附后的抗Hu抗体阳性患者血清。结果添加抗Hu抗体阳性PNS患者血清IgG的培养神经细胞互相融合,由粗而长的突起相互连接,而对照组未看到上述变化。各组均未发现凋亡的神经细胞。结论抗Hu抗体未能引起神经细胞的凋亡或死亡,推测是诱导了接触因子的表达促进了细胞的分化。     

抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义

目的 探讨抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义.方法 采用间接免疫荧光方法和蛋白免疫印迹法对送检至北京协和医院神经病理实验室的1500余例患者的血清和脑脊液进行抗Hu抗体检测,回顾性分析抗Hu抗体阳性患者的临床资料及诊断.神经系统副肿瘤综合征的诊断标准参照Graus等的诊断标准.结果 共有27例患者抗体阳性,其中血清抗Hu抗体阳性25例,脑脊液抗Hu抗体阳性8例.临床主要表现为感觉神经元神经病、亚急性小脑变性、Lambert-Eaton综合征和抗利尿激素分泌不当综合征引起的脑病等,其中20例(74.1%)患有肿瘤,包括肺癌17例,胃癌2例,不明性质腹部肿瘤1例.7例患者未发现恶性肿瘤,包括多发性肌炎和系统性红斑狼疮(SLE)合并神经肌肉病各1例.根据Graus等神经系统副肿瘤综合征的诊断标准,27例中22例可确诊神经系统副肿瘤综合征或相关的肿瘤,抗Hu抗体的阳性预测值为81.5%.结论 抗Hu抗体阳性对神经系统副肿瘤综合征的诊断具有一定意义;其相关肿瘤以肺癌,特别是小细胞肺癌最常见.其他自身免疫性疾病偶可见抗Hu抗体阳性,需要全面检查和密切随访以排除恶性肿瘤的可能.     

抗amphiphysin抗体、抗Hu抗体双阳性副肿瘤神经综合征(附1例报告及文献复习)

目的 提高临床医生对抗amphiphysin抗体、抗Hu抗体双阳性副肿瘤神经综合征的认知.方法 回顾分析1例抗amphiphysin抗体、抗Hu抗体双阳性的副肿瘤神经综合征患者的临床表现、检查及诊疗经过等资料,结合文献复习加以讨论.结果 患者男性,71岁.主要临床表现为进行性肢体无力加重,脑脊液检查抗amphiphys...     

14例抗Hu抗体阳性神经系统副肿瘤综合征临床特征分析

目的 探讨抗Hu抗体阳性神经系统副肿瘤综合征(PNS)的临床特征。方法 收集2016年1月至2020年9月郑州大学第一附属医院收治的抗Hu抗体阳性的确诊PNS的患者,均依据2021年副肿瘤综合征更新诊断标准及PNS诊断评分系统(PNS-Care Score)进行诊断。患者均随访至2021年8月,分析其临床表现、治疗及预后。结果 共收入14例PNS患者,男8例、女6例,年龄42～74岁,平均(58.93±9.50)岁。14例PNS患者中表现为周围神经病9例(64.3%),其中7例(50.0%)为感觉运动神经病、2例(14.3%)为感觉神经元病,表现为边缘性脑炎和快速进展性小脑综合征各2例(14.3%)、脑干脑炎1例(7.1%);合并小细胞肺癌11例(78.6%),乳腺癌、胸腺瘤及B细胞淋巴瘤各1例(7.1%)。14例中11例(78.6%)在肿瘤确诊之前出现神经系统症状,延迟诊断15 d至14个月,中位延迟时间为4.00(2.00,6.00)个月。14例PNS患者中,8例接受肿瘤治疗,8例接受免疫治疗,其中甲泼尼龙冲击6例、丙种球蛋白治疗2例,3例仅接受对症治疗;3例病情好转,11例死亡。...     

特异性神经元抗核抗体—Hu抗体的研究

为探讨Ｈｕ抗体在神经系统副肿瘤综合征（ＰＮＳＮＳ）发病中的作用。用亲合免疫细胞组织化学ＡＢＣ法及免疫印迹技术测定１７例患者血清、脑脊液及尿液中的Ｈｕ抗体。结果显示１７例患者血清中Ｈｕ抗体滴度为１∶１０００至１∶６４０００；脑脊液（１５例）中滴度为１∶１０～１∶４０００；尿液（５例）中滴度为１∶２０～１∶２００。Ｈｕ抗体识别的抗原分子量为３５～４０万。提示Ｈｕ抗体是与ＰＮＳＮＳ有关的一种高度特异性自身抗体，ＰＮＳＮＳ可能为一种自身免疫性疾病，Ｈｕ抗体在致病过程中起重要作用。     

多脑神经并感觉运动神经广泛受累的抗Hu抗体相关神经副肿瘤综合征一例

1 病例报告 患者女,57岁.因"四肢麻木、视物成双9个月,加重伴步态不稳、饮水呛咳3个月余"于2019-09-24入院.9个月前因"上呼吸道感染"后出现双手麻木、视物成双,渐发展到四肢麻木,右侧肢体较左侧明显,行走尚可.3个月前开始出现步态不稳、饮水呛咳、声音嘶哑.无头晕、头痛,无大小便障碍,无汗腺分泌异常等.     

5年随访未见肿瘤发生的抗Hu抗体阳性副肿瘤综合征1例

神经系统副肿瘤综合征(paraneoplastic neurological syndrome, PNS)是指由恶性肿瘤继发的自身免疫反应而导致中枢神经系统、周围神经系统、自主神经系统或肌肉损害的临床症候群。PNS临床少见, 仅约1%的成年恶性肿瘤患者并发PNS[1]。约79.4%的患者神经系统症状早于肿瘤发现, 肿瘤确诊晚于PNS的平均时间为20个月, 但有的病例超过5年随访仍未见肿瘤发生[1,2]。另外, PNS中伴听力损害的病例极少, 目前国内外仅见个案报道。笔者现报告1例伴听力下降的5年随访仍未发现肿瘤的PNS患者的临床资料和诊治过程, 并回顾相关文献, 以期为临床工作者提供参考。     

神经系统副肿瘤综合征与神经副肿瘤抗体分析

目的探讨神经系统副肿瘤综合征(PNS)临床表现及神经副肿瘤抗体的特征。方法分析2009年1月至2019年9月北京大学第一医院神经内科确诊的110例PNS患者的临床特征及神经副肿瘤抗体类型。结果110例患者出现17种临床综合征,其中43例(39.1%)为经典临床综合征,最常见的为亚急性小脑变性14例(12.7%)和边缘性脑炎11例(10.0%);62例(56.4%)为非经典临床综合征,最常见的为感觉运动周围神经病19例(17.3%)和重症肌无力10例(9.1%)。69例(62.7%)患者发现恶性肿瘤,肺癌20例(18.2%)及血液系统肿瘤12例(10.9%)为最常见的肿瘤。71例(64.5%)患者在血液中检测到特征性副肿瘤抗体,最常见的为抗Amphiphysin抗体26例(23.6%)和抗Yo抗体24例(21.8%)。结论临床表现为非经典副肿瘤综合征的患者,亦应积极进行特征性副肿瘤抗体的检测,并根据抗体结果对特定肿瘤进行重点筛查。     

抗体及副肿瘤综合征相关的运动障碍

抗体及副肿瘤综合征相关的运动障碍越来越被重视,其症状的出现对诊断具有一定的提示意义,而症状多样性常被忽视.本文综述了肿瘤有关的抗体与运动障碍的关系,这些运动障碍除副肿瘤性共济失调、眼阵挛-肌阵挛综合征外,还包括舞蹈症、肌张力障碍、震颤、快动眼睡眠行为障碍、僵人综合征和帕金森综合征等常见的运动障碍.这类运动障碍可理解为自...     

抗-Amphiphysin抗体与神经系统副肿瘤综合征的免疫学研究

目的探讨抗神经元突触囊泡Ａｍｐｈｉｐｈｙｓｉｎ抗体（抗Ａｍｐｈｉｐｈｙｓｉｎ抗体）在神经系统副肿瘤综合征（ＰＮＳＮＳ）发病机制中的作用及与癌肿的关系。方法应用免疫印迹技术测定３９０例小细胞肺癌（ＳＣＬＣ）１０３例其他癌肿及１０４例非ＰＮＳＮＳ的神经系统疾病患者血清中抗Ａｍｐｈｉｐｈｙｓｉｎ抗体。结果１１例ＳＣＬＣ患者血清中存在抗Ａｍｐｈｉｐｈｙｓｉｎ抗体，其中８例伴有ＰＮＳＮＳ。抗Ａｍｐｈｉｐｈｙｓｉｎ抗体识别脑神经元提取物中抗原相对分子量分子量１２５万的蛋白带。结论抗Ａｍｐｈｉｐｈｙｓｉｎ抗体是一种与ＰＮＳＮＳ及ＳＣＬＣ有关的神经元自身抗体，检测此种抗体对于ＰＮＳＮＳ及ＳＣＬＣ的临床诊断及治疗有一定的意义     

Effects of antineuronal antibodies from patients with paraneoplastic neurological syndrome on primary-cultured neurons

Some patients with paraneoplastic neurological syndrome (PNS) produce autoantibodies against tumor and neuronal tissues of symptom-relevant areas. These characteristic antibodies are detected at early stages of the neurological disorder and are reliable markers for the diagnosis of PNS and underlying cancers. These antibodies are thought to be related directly to neuronal damage. However, the passive transfer of antibodies to rodents has been succeeded only in those in which the target antigens were expressed on the cell surface, like Lambert-Eaton myasthenic syndrome. The serum IgGs from patients with PNS and anti-Yo or anti-Hu antibody were not shown to induce the disease by passive transfer or active immunization with these antigen proteins to date. Instead, cytotoxic T lymphocytes (CTLs) against these antigen peptides-presenting targets could be induced in the peripheral blood of PNS patients. However, there is no direct proof of CTLs killing neurons. In this study, we examined the effects of the anti-Yo or anti-Hu antibody on mouse-brain-derived neurons in a primary culture system and found that these antibodies did not kill neurons, but induced the expression of cell adhesion molecules and accelerated neuronal differentiation. These effects of serum IgG fractions containing the anti-Yo or the anti-Hu antibody on the cultured neurons were the same, suggesting that their effects were not through the binding of the antibody to specific antigens, but to some other factors contained in IgG fractions.     

Multiple paraneoplastic syndromes in a patient with antibodies to neuronal nucleoproteins (anti-Hu)

We report the clinical and autopsy studies of a patient with an unusual combination of multiple paraneoplastic neurological syndromes in association with antibodies to a 35–40 kDa neuronal nucleoprotein (anti-Hu). Neurological disease preceded the detection of a small cell carcinoma of the lung. The patient had combined sensory and motor neuronopathy or neuropathy, cerebellar degeneration, brain-stem and limbic encephalitis, and clinical evidence of the Lambert-Eaton myasthenic syndrome and gastrointestinal pseudo-obstruction of paraneoplastic origin.     

神经系统副肿瘤综合征临床分析

目的探讨神经系统副肿瘤综合征的临床特征及诊断方法,提高对副肿瘤综合征的认识。方法对2011-12我院收治的神经系统副肿瘤综合征患者临床资料进行分析,并复习相关文献。结果该病临床及影像学无特异性,目前诊断主要依据临床、影像学及实验室检查。结论临床上遇到治疗效果不佳的类似吉兰-巴雷综合征患者时应注意检查有无恶性肿瘤。     

神经系统副肿瘤综合征34例临床特点分析

目的:分析34例神经系统副肿瘤综合征患者的临床特点。方法:对1990年至2005年收治的34例神经系统副肿瘤综合征患者的临床资料进行回顾性分析。结果:副肿瘤综合征的临床类型有周围神经病15例、Lambert-Eaton肌无力综合征5例、多发性肌炎和皮肌炎3例、进行性小脑变性2例、运动神经元病3例、进行性多灶性白质脑病1例、亚急性坏死性脊髓病1例、脑干脑炎2例、边缘系统脑炎2例。结论:神经系统副肿瘤综合征临床表现形式多样,容易误诊,临床早期确诊对于隐匿肿瘤的发现和治疗非常重要。     

北京协和医院1990～2000年副肿瘤综合征住院病例总结

目的　了解副肿瘤综合征 2 6例患者的临床基本特征。方法　回顾性分析 1990～ 2 0 0 0年北京协和医院副肿瘤综合征患者的临床资料并加以总结。结果　副肿瘤综合征平均发病年龄 4 8.6± 2 6岁 ,男性占 6 9.2 % ,女性占 30 .8%。 3.8%患者在发现肿瘤后才出现神经症状 ;96 .2 %在出现副肿瘤症状后才发现肿瘤。诊断出副肿瘤综合征时 ,2 6 .9%肿瘤已出现转移。从出现神经症状至发现肿瘤平均时间为 18± 6个月 ,患者多为慢性隐袭或亚急性起病 ,症状进行性加重 ,对治疗无明显缓解。结论　副肿瘤综合征出现明显的临床症状可发生在肿瘤发现之前、之后或与之同时发生 ,它们的出现几乎均预示预后不良。临床早期诊断对于及时发现和治疗癌肿至关重要     

Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic neurological disease

Sera from 23 patients with paraneoplastic disease of the central nervous system (PNS) were examined for the presence of anti-neuronal (anti-Hu, anti-Yo/PCA) and anti-Ri) and systemic auto-antibodies, including antibodies against DNA, centromeres, nRNP, Sm antigen, Scl-70, Ro(SS-A), La(SS-B), mitochondria, thyroid antigens, parietal calls, brush border antigen and rheumatoid factor. As controls, sera from 33 patients with small cell lung cancer, 33 with ovarian cancer and 7 with breast cancer and from 107 aged-matched healthy persons were used. Systemic auto-antibodies were found in 52% of patients with para-neoplastic neurological syndromes compared with only 16% (P = 0.001) in the control group with cancer only and 15% in the group of healthy controls. The relatively high percentage of systemic auto-antibodies in patients with PNS indicates that there is a genetic susceptibility to the development of auto-immune phenomena. This may provide an explanation for the relatively rare occurrence of PNS in patients with cancer.     

Disturbance in the serum IgG subclass distribution in patients with anti-Hu positive paraneoplastic neurological syndromes

Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti-Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme-linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti-Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti-Hu antibody seems to be independent from this phenomenon.     

脑苷肌肽对体外培养神经元BDNF表达的影响

目的 研究脑苷肌肽（CM1）对培养神经元脑源性神经营养因子（BDNF）的表达及其意义。方法 培养液加入一定剂量的CM1，利用免疫组织化学方法检测无血清培养神经元BDNF的表达。结果 CM1可促进神经元的生长发育，明显增加BDNF免疫阳性细胞的表达。结论 CM1在神经元生长发育中可能具有重要作用。