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d-serine prevents cognitive impairment in a mouse model of NMDAR encephalitis d-丝氨酸可预防NMDAR脑炎小鼠模型的认知损伤
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.jneuroim.2025.578768
Hanyu Luo, Ziyao Han, Jiaxin Yang, Xiaoyue Yang, Yuhang Li, Dishu Huang, Ran Ding, Li Cheng, Jiannan Ma, Li Jiang

Objective

Despite effective immunotherapy, many patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis continue to have persistent cognitive deficits. This study investigated whether d-serine administration can ameliorate cognitive impairment in a mouse model of anti-NMDAR encephalitis.

Methods

Mice received continuous intracerebroventricular infusions of purified IgG isolated from pooled cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis or non-inflammatory controls for 14 days. During the same period, mice were given daily intraperitoneal injections of d-serine or saline. Cognitive function and hippocampal synaptic plasticity were evaluated using a battery of behavioral tests and long-term potentiation (LTP) recordings. Western blotting and immunofluorescence staining were used to evaluate hippocampal NMDAR clustering and activation of the CaMKII/ERK/CREB pathway.

Results

After 14 days, mice infused with patient-derived anti-NMDAR antibodies showed significant memory impairment and reduced hippocampal LTP. These deficits were markedly attenuated by concurrent d-serine treatment. Patient-derived anti-NMDAR antibodies reduced synaptic NMDAR clusters and membrane NMDAR1 expression in hippocampus, whereas d-serine administration produced only a modest, non-significant increase in these measures. In contrast, d-serine significantly restored phosphorylation of CaMKII, ERK, and CREB that was suppressed by anti-NMDAR antibodies.

Conclusion

d-serine effectively ameliorates cognitive impairment induced by anti-NMDAR antibodies, likely by restoring NMDAR-mediated CaMKII/ERK/CREB signaling. These findings support d-serine as a potential adjunct to immunotherapy for patients with anti-NMDAR encephalitis.
尽管有有效的免疫治疗,许多抗n -甲基-d-天冬氨酸受体(NMDAR)脑炎患者仍然存在持续的认知缺陷。本研究探讨d-丝氨酸是否可以改善抗nmdar脑炎小鼠模型的认知障碍。方法将抗nmdar脑炎患者或非炎症对照组脑脊液中分离的纯化IgG连续脑室输注14天。在同一时期,小鼠每天腹腔注射d-丝氨酸或生理盐水。认知功能和海马突触可塑性通过一系列行为测试和长期增强(LTP)记录进行评估。采用Western blotting和免疫荧光染色评价海马NMDAR聚集和CaMKII/ERK/CREB通路的激活情况。结果注射患者源性抗nmdar抗体14天后,小鼠出现明显的记忆障碍和海马LTP降低。同时使用d-丝氨酸治疗可显著减轻这些缺陷。患者源性抗NMDAR抗体降低了突触NMDAR簇和海马膜NMDAR1的表达,而d-丝氨酸只产生了适度的、不显著的增加。相反,d-丝氨酸显著恢复了被抗nmdar抗体抑制的CaMKII、ERK和CREB的磷酸化。结论-丝氨酸可能通过恢复nmdar介导的CaMKII/ERK/CREB信号通路,有效改善抗nmdar抗体诱导的认知功能障碍。这些发现支持d-丝氨酸作为抗nmdar脑炎患者免疫治疗的潜在辅助药物。
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引用次数: 0
The visual outcome and efficacy of current therapies for neurosarcoidosis with anterior visual pathway involvement: A systemic review 目前治疗前视觉通路受累的神经结节病的视觉效果和疗效:一项系统综述。
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-27 DOI: 10.1016/j.jneuroim.2025.578761
Xia Zhang , Xinyu Zhao , Bo Chen , Lukasz Lagojda , Eva Oustabassidis , Tarunya Arun , Srilakshmi Sharma

Purpose

To examine the clinical characteristics of neurosarcoidosis with anterior visual pathway involvement (NSAVP), assess the effectiveness of current treatments, and provide insights into the demographics, symptoms, and treatment outcomes to better guide clinical management of NSAVP.

Methods

The databases PubMed, Embase, MEDLINE, CINAHL and Ovid were searched to identify relevant studies. Statistical analyses were performed in R.

Results

Thirty-three studies involving 334 patients and 404 eyes were included in the meta-analysis. Our findings indicate that NSAVP predominantly affects females. Bilateral involvement was observed in 46 % of cases. Visual loss was the most common presenting symptom, affecting 94 % of patients; 78 % had no prior symptoms of systemic involvement. Three percent had isolated AVP manifestations. Fewer than 17 % had co-existing orbital or cranial nerve signs and 29 % had co-existing uveitis.
Sixty-three percent had an MRI abnormality of the AVP. The most frequently reported laboratory abnormality was an elevated white cell count in cerebrospinal fluid (CSF), followed by elevated protein in CSF and elevated serum ACE level.
Following treatment, 57 % experienced visual improvement. The visual improvement rate was similar for patients receiving steroids alone (46 %) and those receiving combined steroid and immunosuppressive therapy (44 %). Combined therapy was associated with a lower the incidence of no light perception (NLP, 1 % vs. 16 %), a higher proportion with vision better than 20/200 (70 % vs. 62 %) and a lower incidence of relapse (16 % vs. 40 %).

Conclusion

NSAVP predominantly affects females, with visual loss being the most common presenting symptom. Combination therapy of steroids and immunosuppressants was associated with better outcomes than steroids alone, including lower incidence of relapse and fewer cases of no light perception.
目的:探讨神经结节病伴前视通路累及(NSAVP)的临床特征,评估当前治疗的有效性,为NSAVP的临床治疗提供人口学特征、症状和治疗效果方面的见解。方法:检索PubMed、Embase、MEDLINE、CINAHL、Ovid等数据库,筛选相关研究。结果:meta分析纳入33项研究,涉及334例患者和404只眼睛。我们的研究结果表明,NSAVP主要影响女性。在46%的病例中观察到双侧受累。视力丧失是最常见的症状,影响了94%的患者;78%之前没有系统性受累的症状。3%有孤立的AVP表现。少于17%的患者同时存在眶神经或颅神经征象,29%的患者同时存在葡萄膜炎。63%的人有AVP的MRI异常。最常报道的实验室异常是脑脊液(CSF)白细胞计数升高,其次是CSF蛋白升高和血清ACE水平升高。治疗后,57%的患者视力得到改善。单独接受类固醇治疗的患者(46%)和接受类固醇和免疫抑制联合治疗的患者(44%)的视力改善率相似。联合治疗与无光感发生率较低(NLP, 1%对16%),视力优于20/200的比例较高(70%对62%)和复发率较低(16%对40%)相关。结论:NSAVP主要影响女性,以视力丧失为最常见的症状。与单独使用类固醇相比,类固醇和免疫抑制剂联合治疗具有更好的预后,包括更低的复发率和更少的无光感病例。
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引用次数: 0
Clinico-pathological correlation in unilateral cortical encephalitis treated with tocilizumab after first-line treatment failure 单侧皮质脑炎一线治疗失败后托珠单抗治疗的临床病理相关性
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jneuroim.2025.578764
Samir Alkabie , Samer Ali , Saeed Asiry , Ana M. Franceschi , Derek Chong , Souhel Najjar

Objectives

To characterize clinico-pathologic findings and therapeutic response in a rare case of unilateral cortical encephalitis successfully treated with tocilizumab after first-line treatment failure, highlighting potential immune mechanisms.

Methods

Case report.

Results

A 49-year-old man developed fever, seizure, and hemicortical deficits. MRI showed right cortical T2-hyperintensity, gyral enhancement, corresponding to 18F-FDG-PET hypermetabolism, compatible with unilateral cortical encephalitis. Extensive metabolic, infectious, and malignancy workup was unrevealing. Neural autoantibodies were negative. 6-months of progressive cognitive decline, visual, speech, and gait disturbance and an infectious event (appendicitis) preceded acute unihemispheric encephalitic syndrome. Brain biopsy demonstrated increased cortical perineuronal microglial activation, retraction of astrocytic processes from microvessels suggestive of blood-brain barrier disruption, and mainly perivascular CD4+T-cell infiltrates, alongside excess circulating interleukin-18 collectively implicating innate and adaptive immune mechanisms. Initial treatment with pulse steroids and intravenous immunoglobulin failed to yield improvement. Tocilizumab as second-line treatment concomitant to weekly pulse steroids led to significant recovery in cognition, gaze deviation, speech, and gait and resolution of imaging abnormalities.

Discussion

Tocilizumab—an IL-6 receptor blocker—was selected given the pleiotropic role of IL-6 in proinflammatory CD4+T-cell differentiation (Th17/Treg imbalance) and innate immune-driven CNS inflammation. This case illustrates the utility of clinico-pathological correlation and cytokine profiling in guiding immunotherapy selection in antibody-negative autoimmune encephalitis.
目的分析1例罕见的单侧皮质脑炎患者在一线治疗失败后,托珠单抗成功治疗的临床病理表现和治疗反应,强调潜在的免疫机制。MethodsCase报告。结果1例49岁男性患者出现发热、癫痫发作和大脑半球功能缺损。MRI示右侧皮质t2高,脑回增强,对应18F-FDG-PET高代谢,与单侧皮质脑炎相符。广泛的代谢、感染和恶性检查未发现。神经自身抗体阴性。6个月进行性认知能力下降、视觉、语言和步态障碍以及感染性事件(阑尾炎)先于急性单半球脑病综合征。脑活检显示皮层神经周围小胶质细胞激活增加,星形细胞过程从微血管撤回提示血脑屏障破坏,主要是血管周围CD4+ t细胞浸润,以及过量的循环白细胞介素-18共同暗示先天和适应性免疫机制。最初使用脉冲类固醇和静脉注射免疫球蛋白治疗未能取得改善。Tocilizumab作为伴随每周脉冲类固醇的二线治疗导致认知,凝视偏差,言语和步态的显着恢复以及成像异常的解决。考虑到IL-6在促炎性CD4+ t细胞分化(Th17/Treg失衡)和先天免疫驱动的中枢神经系统炎症中的多效性作用,我们选择了IL-6受体阻断剂tocilizumab。本病例说明了临床病理相关性和细胞因子谱在指导抗体阴性自身免疫性脑炎免疫治疗选择中的作用。
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引用次数: 0
Rheumatoid meningitis presented as recurrent stroke-like symptoms: A case report and literature review 类风湿性脑膜炎表现为复发性卒中样症状:1例报告及文献复习
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jneuroim.2025.578763
Xin Yang , Shuping Fang , Zilong Hao , Weihong Kuang

Introduction

Rheumatoid meningitis (RM) presents a diverse array of symptoms that can mimic stroke or transient ischemic attack (TIA), creating significant challenges for early clinical diagnosis.

Methods

This study reported on a patient who presented with recurrent stroke-like symptoms and was diagnosed with RM. Additionally, a literature review was conducted on PubMed using the terms “rheumatoid arthritis,” “central nervous system,” “meningitis,” and “rheumatoid meningitis” on December 20, 2023.

Results

Nineteen patients diagnosed with RM who exhibited stroke-like symptoms or TIA were included in the analysis. Of these, 58 % were male, with a median age of 65 years (range: 37–87 years). The duration of rheumatoid arthritis (RA) varied from 0 to 12 years. Approximately 80 % of patients showed meningeal enhancement on MRI, with 47 % displaying asymmetric enhancement, 21 % diffuse enhancement, and 5 % a mass-like lesion. CSF analysis revealed mild elevations in white blood cell count and protein in 68 % of patients. Biopsies were performed in 13 out of 19 cases, with 11 cases (85 %) showing chronic inflammation, including 10 with leptomeningitis or pachymeningitis, 1 with vasculitis, and 1 with necrotizing granulomatous meningitis. Corticosteroids were the most commonly used treatment.

Conclusion

For patients presenting with stroke-like or TIA symptoms who have a history of RA, it is crucial to consider RM in the differential diagnosis. Further research is needed to determine the most effective treatment strategies for these patients.
类风湿性脑膜炎(RM)表现出多种症状,可模仿中风或短暂性脑缺血发作(TIA),为早期临床诊断带来重大挑战。方法本研究报告了一例反复出现卒中样症状并被诊断为RM的患者。此外,于2023年12月20日在PubMed上使用“类风湿关节炎”、“中枢神经系统”、“脑膜炎”和“类风湿脑膜炎”等术语进行了文献综述。结果本组共纳入了19例表现卒中样症状或TIA的RM患者。其中,58%为男性,中位年龄为65岁(范围:37-87岁)。类风湿关节炎(RA)的病程从0年到12年不等。大约80%的患者MRI表现为脑膜强化,47%为不对称强化,21%为弥漫性强化,5%为肿块样病变。脑脊液分析显示68%的患者白细胞计数和蛋白轻度升高。19例患者中有13例进行了活检,其中11例(85%)表现为慢性炎症,其中10例为轻脑膜炎或厚膜脑膜炎,1例为血管炎,1例为坏死性肉芽肿性脑膜炎。皮质类固醇是最常用的治疗方法。结论对于有RA病史的卒中样或TIA症状患者,鉴别诊断时应考虑RM。需要进一步的研究来确定对这些患者最有效的治疗策略。
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引用次数: 0
Translational Evidence of Immunomodulation by Addictive Drugs: Mechanisms and Therapeutic Targets 成瘾药物免疫调节的转化证据:机制和治疗靶点。
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.jneuroim.2025.578762
Luis M. Tuesta , Cassandra D. Gipson
{"title":"Translational Evidence of Immunomodulation by Addictive Drugs: Mechanisms and Therapeutic Targets","authors":"Luis M. Tuesta ,&nbsp;Cassandra D. Gipson","doi":"10.1016/j.jneuroim.2025.578762","DOIUrl":"10.1016/j.jneuroim.2025.578762","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578762"},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epstein-Barr virus reactivation is associated with altered immune cell profiles in peripheral blood and cerebrospinal fluid of treatment-naive multiple sclerosis patients eb病毒再激活与初治疗多发性硬化症患者外周血和脑脊液中免疫细胞谱的改变有关
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-21 DOI: 10.1016/j.jneuroim.2025.578758
Vasileios Gouzouasis , Margaritis Tsifintaris , Spyros Tastsoglou , Nikos Markoglou , Dimitris Karathanasis , Lila Dimitrakopoulou , Anastasia Dagkonaki , Evangelos Korakidis , George Mpekoulis , Niki Vassilaki , Artemis G. Hatzigeorgiou , Maria Anagnostouli , Maria Eleftheria Evangelopoulos , Antonis Giannakakis , Lesley Probert , Hellenic Academy of Neuroimmunology
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with autoimmune and neurodegenerative components, recently linked with Epstein-Barr virus (EBV) infection. To investigate immunological alterations associated with EBV reactivation (EBV-R) in MS we analyzed immune cell profiles in matched peripheral blood (PB) and cerebrospinal fluid (CSF) samples from treatment-naive MS patients, in relation to plasma EBV serology markers. In our Hellenic MS cohort, 12 of 33 patients (39 %) exhibited serological evidence of EBV-R (VCA IgG+ with VCA IgA+, VCA IgM+, or EA(D) IgG+), and 7 of these 12 also tested positive for plasma BZLF1 mRNA, indicative of lytic infection. EBV-R patients showed reduced CD19+ B cells in PB and equal proportions in CSF compared to patients with latent EBV infection. Conversely, EBV-R patients showed increased cytotoxic CD56dim NK cells and CD14+ monocytes in PB, while cytotoxic CD56dim NK cells remained absent in the CSF, regardless of EBV status. Proportions of regulatory CD56bright NK cells were reduced in both PB and CSF during EBV-R. Our results reveal that MS patients with serological evidence of EBV-R show altered immune responses, with reduced B cell proportions in the PB in the presence of expanded cytotoxic NK cells, and unaffected B cell proportions in CSF in the absence of cytotoxic NK cell surveillance.
多发性硬化症(MS)是一种中枢神经系统慢性炎症性脱髓鞘疾病,具有自身免疫性和神经退行性成分,最近与eb病毒(EBV)感染有关。为了研究与多发性硬化症患者EBV再激活(EBV- r)相关的免疫学改变,我们分析了来自首次治疗的多发性硬化症患者的匹配外周血(PB)和脑脊液(CSF)样本中的免疫细胞谱,以及血浆EBV血清学标志物。在我们的希腊多发性硬化队列中,33例患者中有12例(39%)显示EBV-R (VCA IgG+, VCA IgA+, VCA IgM+或EA(D) IgG+)的血清学证据,其中7例血浆BZLF1 mRNA检测阳性,表明溶血性感染。与潜伏性EBV感染患者相比,EBV- r患者外周血中CD19+ B细胞减少,脑脊液中CD19+ B细胞比例相等。相反,EBV- r患者在PB中显示细胞毒性CD56dim NK细胞和CD14+单核细胞增加,而在脑脊液中仍然没有细胞毒性CD56dim NK细胞,无论EBV状态如何。EBV-R期间,PB和CSF中调节性CD56bright NK细胞的比例均降低。我们的研究结果显示,具有EBV-R血清学证据的MS患者表现出免疫反应的改变,在细胞毒性NK细胞扩增的情况下,PB中的B细胞比例降低,而在没有细胞毒性NK细胞监测的情况下,CSF中的B细胞比例不受影响。
{"title":"Epstein-Barr virus reactivation is associated with altered immune cell profiles in peripheral blood and cerebrospinal fluid of treatment-naive multiple sclerosis patients","authors":"Vasileios Gouzouasis ,&nbsp;Margaritis Tsifintaris ,&nbsp;Spyros Tastsoglou ,&nbsp;Nikos Markoglou ,&nbsp;Dimitris Karathanasis ,&nbsp;Lila Dimitrakopoulou ,&nbsp;Anastasia Dagkonaki ,&nbsp;Evangelos Korakidis ,&nbsp;George Mpekoulis ,&nbsp;Niki Vassilaki ,&nbsp;Artemis G. Hatzigeorgiou ,&nbsp;Maria Anagnostouli ,&nbsp;Maria Eleftheria Evangelopoulos ,&nbsp;Antonis Giannakakis ,&nbsp;Lesley Probert ,&nbsp;Hellenic Academy of Neuroimmunology","doi":"10.1016/j.jneuroim.2025.578758","DOIUrl":"10.1016/j.jneuroim.2025.578758","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with autoimmune and neurodegenerative components, recently linked with Epstein-Barr virus (EBV) infection. To investigate immunological alterations associated with EBV reactivation (EBV-R) in MS we analyzed immune cell profiles in matched peripheral blood (PB) and cerebrospinal fluid (CSF) samples from treatment-naive MS patients, in relation to plasma EBV serology markers. In our Hellenic MS cohort, 12 of 33 patients (39 %) exhibited serological evidence of EBV-R (VCA IgG+ with VCA IgA+, VCA IgM+, or EA(D) IgG+), and 7 of these 12 also tested positive for plasma <em>BZLF1</em> mRNA, indicative of lytic infection. EBV-R patients showed reduced CD19+ B cells in PB and equal proportions in CSF compared to patients with latent EBV infection. Conversely, EBV-R patients showed increased cytotoxic CD56<sup>dim</sup> NK cells and CD14<sup>+</sup> monocytes in PB, while cytotoxic CD56<sup>dim</sup> NK cells remained absent in the CSF, regardless of EBV status. Proportions of regulatory CD56<sup>bright</sup> NK cells were reduced in both PB and CSF during EBV-R. Our results reveal that MS patients with serological evidence of EBV-R show altered immune responses, with reduced B cell proportions in the PB in the presence of expanded cytotoxic NK cells, and unaffected B cell proportions in CSF in the absence of cytotoxic NK cell surveillance.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578758"},"PeriodicalIF":2.5,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Live MOG-IgG cell-based assay: Comparison across flow cytometers and diagnostic validation on high-sensitivity full spectrum flow cytometry 基于活MOG-IgG细胞的检测:流式细胞仪的比较和高灵敏度全谱流式细胞仪的诊断验证
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-17 DOI: 10.1016/j.jneuroim.2025.578760
Elisha Siwan , Asawin Tungpoomjaruswong , Vera Merheb , Fiona X.Z. Lee , Fakhria Kakar , Mark Acebes , Russell C Dale , David McDonald , Sudarshini Ramanathan , Ming-Wei Lin , David A Brown , Fabienne Brilot
MOG antibody-associated disease (MOGAD) diagnosis rests on seropositivity for MOG antibody (MOG-IgG). Live cell-based assays (CBA) are gold standards. Although flow cytometry live CBAs have high real-world sensitivity, their global implementation and diagnostic deployment have been challenged by perceptions of “in-house” design and custom optimization. Herein, we compared the analytical robustness of flow live MOG-IgG CBA across various cytometers in both research and diagnostic laboratories. Flow live CBAs were performed on three conventional (Fortessa, BDLSRII, Gallios), and two spectral cytometers (Aurora, ID7000). MOG-IgG titers were calculated by median fluorescence intensity (MFI), and intra- and inter assay precisions (CV%) and serostatuses were determined. The MFI detection range on Fortessa, currently used for testing, was significantly lower than spectral ID7000 (4.75-fold, p = 0.04) and Aurora (12-fold, p = 0.0001), albeit all MFIs correlated (p < 0.0001; R2 = 0.99). Interestingly, the high detection range was attributed to technology, not laboratory environments (p > 0.05). Intra- and inter-assay precisions were similar across cytometers. ID7000 and Fortessa had the lowest variation, with 4.6 % and 6.8 % intra-CV, respectively, and 15.7 % inter-CV. FACS ratio, currently reported as MOG-IgG titre, and MFIs were comparable and correlated for all cytometers (p < 0.001; R2 ≤ 0.99), regardless of the analysis software (p < 0.0001, R2 = 0.98). All serostatuses were highly concordant (κ = 1). Our results demonstrate that flow live CBAs can be validated in diagnostic laboratories across a range of flow cytometers with high reproducibility and repeatability. In particular, excellent assay performance on spectral flow cytometry strongly supports the proof-of-concept use of this technology for diagnostic purposes.
MOG抗体相关疾病(MOGAD)的诊断依赖于MOG抗体(MOG- igg)的血清阳性。基于活细胞的检测(CBA)是金标准。尽管流式细胞术活体cba具有很高的真实世界灵敏度,但其全球实施和诊断部署受到“内部”设计和定制优化观念的挑战。在此,我们比较了流动活MOG-IgG CBA在研究和诊断实验室的各种细胞仪上的分析稳健性。流式活cba在三台常规(Fortessa, BDLSRII, Gallios)和两台光谱细胞仪(Aurora, ID7000)上进行。用中位荧光强度(MFI)计算MOG-IgG滴度,测定测定内、间精密度(CV%)和血清状态。目前用于检测的Fortessa上的MFI检测范围明显低于光谱ID7000(4.75倍,p = 0.04)和Aurora(12倍,p = 0.0001),尽管所有MFI都相关(p < 0.0001; R2 = 0.99)。有趣的是,高检测范围归因于技术,而不是实验室环境(p > 0.05)。在不同的细胞仪中,测定内和测定间的精密度相似。ID7000和Fortessa变异最小,cv内变异率分别为4.6%和6.8%,cv间变异率分别为15.7%。无论使用什么分析软件(p < 0.0001, R2 = 0.98),所有细胞仪的FACS比率(目前报道为MOG-IgG滴度)与mfi具有可比性和相关性(p < 0.001; R2≤0.99)。所有血清状态高度一致(κ = 1)。我们的研究结果表明,流动活cba可以在诊断实验室通过一系列流式细胞仪进行验证,具有高再现性和可重复性。特别是,光谱流式细胞术的优异分析性能有力地支持了该技术用于诊断目的的概念验证。
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引用次数: 0
Corneal neuro-immune crosstalk in Fabry disease: An in vivo confocal microscopic study 法布里病的角膜神经免疫串扰:体内共聚焦显微镜研究
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-16 DOI: 10.1016/j.jneuroim.2025.578759
Xuecong Zhou , Yingsi Li , Yawen Zhao , Xiaoming Yan , Wei Zhang , Yuan Wu

Purpose

This study aims to assess the corneal nerve damage and corneal immune alteration by in vivo confocal microscopy (IVCM) in Fabry disease (FD)

Methods

Sixty-two eyes from 31 patients with FD were analysed and compared with fifty eyes from 25 healthy controls in this prospective, cross-sectional, controlled, single-center study. After evaluating corneal sensation by the Cochet-bonnet esthesiometer, the IVCM was performed to evaluate the sub-basal nerve plexus (CSNP) including density, number, tortuosity and reflectivity of corneal nerve, and the inflammatory cells including mature/immature Langerhans cells (LCs) and leukocytes. The differences between FD and healthy controls, different genders (heterozygous and hemizygous), phenotypes (classical, nonclassical) and Mainz severity score index (MSSI) scores were compared

Results

A significant reduction of corneal nerve density, number and reflectivity, as well as an increase of tortuosity occurred in the FD group compared with healthy controls (P < 0.001). The density of LCs was significantly increased in the FD group compared with the healthy controls in the central cornea (P = 0.016) and peripheral cornea (P < 0.001). The more severe corneal neuropathy and higher density of LCs were found in hemizygous males than heterozygous females (P < 0.05). As for the difference between distinct phenotypes and MSSI scores, we did not find significant difference in corneal nerve parameters and LCs density

Conclusions

IVCM provides parameters that reliably indicate corneal nerve damage and inflammatory activation in patients with FD
目的利用体内共聚焦显微镜(IVCM)观察法布里病(FD)患者角膜神经损伤及角膜免疫功能改变。方法采用前瞻性、横断面、对照、单中心研究,对31例FD患者62只眼进行分析,并与25例健康对照者50只眼进行比较。在用Cochet-bonnet感觉仪评估角膜感觉后,采用IVCM评估基底下神经丛(CSNP),包括角膜神经的密度、数量、弯曲度和反射率,以及炎症细胞包括成熟/未成熟朗格汉斯细胞(LCs)和白细胞。比较FD组与健康对照组、不同性别(杂合子和半合子)、表型(经典型、非经典型)和Mainz严重性评分指数(MSSI)评分的差异。结果FD组与健康对照组相比,角膜神经密度、数量和反射率显著降低,扭曲度显著增加(P < 0.001)。与健康对照组相比,FD组角膜中央(P = 0.016)和周围(P < 0.001)的LCs密度显著增加。半合子男性比杂合子女性角膜神经病变更严重,LCs密度更高(P < 0.05)。对于不同表型和MSSI评分之间的差异,我们没有发现角膜神经参数和LCs密度有显著差异。结论sivcm提供了可靠的FD患者角膜神经损伤和炎症激活的参数
{"title":"Corneal neuro-immune crosstalk in Fabry disease: An in vivo confocal microscopic study","authors":"Xuecong Zhou ,&nbsp;Yingsi Li ,&nbsp;Yawen Zhao ,&nbsp;Xiaoming Yan ,&nbsp;Wei Zhang ,&nbsp;Yuan Wu","doi":"10.1016/j.jneuroim.2025.578759","DOIUrl":"10.1016/j.jneuroim.2025.578759","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to assess the corneal nerve damage and corneal immune alteration by <em>in vivo</em> confocal microscopy (IVCM) in Fabry disease (FD)</div></div><div><h3>Methods</h3><div>Sixty-two eyes from 31 patients with FD were analysed and compared with fifty eyes from 25 healthy controls in this prospective, cross-sectional, controlled, single-center study. After evaluating corneal sensation by the Cochet-bonnet esthesiometer, the IVCM was performed to evaluate the sub-basal nerve plexus (CSNP) including density, number, tortuosity and reflectivity of corneal nerve, and the inflammatory cells including mature/immature Langerhans cells (LCs) and leukocytes. The differences between FD and healthy controls, different genders (heterozygous and hemizygous), phenotypes (classical, nonclassical) and Mainz severity score index (MSSI) scores were compared</div></div><div><h3>Results</h3><div>A significant reduction of corneal nerve density, number and reflectivity, as well as an increase of tortuosity occurred in the FD group compared with healthy controls (<em>P</em> &lt; 0.001). The density of LCs was significantly increased in the FD group compared with the healthy controls in the central cornea (<em>P</em> = 0.016) and peripheral cornea (<em>P</em> &lt; 0.001). The more severe corneal neuropathy and higher density of LCs were found in hemizygous males than heterozygous females (<em>P</em> &lt; 0.05). As for the difference between distinct phenotypes and MSSI scores, we did not find significant difference in corneal nerve parameters and LCs density</div></div><div><h3>Conclusions</h3><div>IVCM provides parameters that reliably indicate corneal nerve damage and inflammatory activation in patients with FD</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578759"},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of autophagy in chronic pain 自噬在慢性疼痛中的作用
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-13 DOI: 10.1016/j.jneuroim.2025.578757
Fu-qi Zhu , Wen-jun Zhang , Bao-zhu Guan
Pain is the biggest factor affecting patients' daily life, and how to alleviate patients' pain and prevent it from developing into chronic pain has always been a key therapeutic goal for clinicians. There are three main causes of chronic pain, which are inflammation, nerve and tumor. And autophagy, as an important pathway to maintain homeostasis of the organism, not only affects the normal autophagy function, but also plays an important role in anti-inflammation, maintenance of nerve cell homeostasis, and inhibition of cancer occurrence and metastasis. Based on the above characteristics, we believe that autophagy has great potential in reducing and avoiding chronic pain. In this paper, after introducing chronic pain and autophagy-related genes, we delve into the pathological mechanisms of chronic pain generation, search for the relationship between autophagy and the three major causes of chronic pain, and find that autophagy may have a powerful therapeutic effect in reducing pain. We believe that autophagy can be a new target for the treatment of chronic pain.
疼痛是影响患者日常生活的最大因素,如何缓解患者的疼痛,防止其发展为慢性疼痛一直是临床医生关注的重点治疗目标。引起慢性疼痛的原因主要有三种,分别是炎症、神经和肿瘤。而自噬作为维持机体内稳态的重要途径,不仅影响机体正常的自噬功能,而且在抗炎、维持神经细胞内稳态、抑制肿瘤发生和转移等方面也发挥着重要作用。基于以上特点,我们认为自噬在减轻和避免慢性疼痛方面具有巨大的潜力。本文在介绍慢性疼痛和自噬相关基因的基础上,深入探讨慢性疼痛产生的病理机制,寻找自噬与慢性疼痛的三大病因之间的关系,发现自噬在减轻疼痛方面可能具有强大的治疗作用。我们相信自噬可以成为治疗慢性疼痛的新靶点。
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引用次数: 0
Neuronal inflammation-associated biomarkers in cerebrospinal fluid of patients with acute and chronic inflammatory demyelinating polyneuropathies 急性和慢性炎症性脱髓鞘性多神经病变患者脑脊液中神经元炎症相关生物标志物
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-11 DOI: 10.1016/j.jneuroim.2025.578756
Ümit Atasever , Canan Akünal , Hayriye Soytürk

Background

Immune-mediated polyneuropathies such as acute and chronic inflammatory demyelinating polyneuropathy are challenging to diagnose and treat effectively.

Objective

To investigate the diagnostic value of certain biomarkers associated with neuronal inflammation in patients with inflammatory demyelinating polyneuropathy.

Methods

Medical records of patients who presented to the Neurology Clinic of BAİBÜ Education and Research Hospital between December 2023 and October 2024 and underwent lumbar puncture (LP) for diagnostic purposes were retrospectively reviewed. CSF samples and clinical data of 20 AIDP patients, 18 CIDP patients, and 15 patients with pseudotumor cerebri (PTC), included as the unhealthy control group, were analyzed.

Results

The CSF levels of NfL, NfH, GFAP, SM, and BDNF in the AIDP group were significantly higher than those in the PTC group (p < 0.05). In the CIDP group, CSF NfL, GFAP, and SM levels were significantly elevated compared to the PTC group (p < 0.05), while no significant difference was observed in CSF NfH and BDNF levels between the CIDP and PTC groups. Furthermore, the AIDP group had significantly higher levels of NfH and BDNF in CSF compared to the CIDP group (p < 0.05).

Conclusions

These findings suggest that in AIDP and CIDP patients, the elevation of CSF NfL, NfH, and GFAP levels may be associated with secondary proximal axonal damage. Additionally, SM could serve as an indicator of myelin breakdown and remodeling, while the compensatory effect of BDNF may support remyelination. In conclusion, these five biomarkers may represent promising targets for the early diagnosis and differential diagnosis of AIDP and CIDP.
免疫介导的多神经病变如急性和慢性炎症性脱髓鞘多神经病变是诊断和有效治疗的挑战。目的探讨与神经炎症相关的生物标志物在炎性脱髓鞘性多发性神经病中的诊断价值。方法回顾性分析2023年12月至2024年10月在BAİBÜ教研院神经内科就诊并行腰椎穿刺诊断的患者病历。分析20例AIDP患者、18例CIDP患者和15例假性脑瘤(PTC)患者作为不健康对照组的脑脊液样本及临床资料。结果AIDP组脑脊液中NfL、NfH、GFAP、SM、BDNF水平显著高于PTC组(p < 0.05)。与PTC组相比,CIDP组脑脊液NfL、GFAP和SM水平显著升高(p < 0.05),而CIDP组与PTC组脑脊液NfH和BDNF水平无显著差异。此外,AIDP组脑脊液中NfH和BDNF水平显著高于CIDP组(p < 0.05)。结论AIDP和CIDP患者脑脊液NfL、NfH和GFAP水平升高可能与继发性近端轴突损伤有关。此外,SM可以作为髓磷脂分解和重塑的指标,而BDNF的代偿作用可能支持髓鞘再生。综上所述,这五种生物标志物可能是AIDP和CIDP早期诊断和鉴别诊断的有希望的靶点。
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Journal of neuroimmunology
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