Journal of neuroimmunology最新文献_第2页

Antibodies in Creutzfeldt-Jakob disease: A systematic review of patient characteristics, diagnostics, and clinical implications 克雅氏病的抗体：对患者特征、诊断和临床意义的系统回顾。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-14 DOI: 10.1016/j.jneuroim.2026.578865

Raluca Bilavu , Marius Benta , Amalia Cornea , Lucian Vasiluta , Elena Cecilia Rosca

Background

Creutzfeldt–Jakob disease (CJD) is a rare, rapidly progressive prion neurodegenerative disorder causing fatal dementia. Recently, reports have identified various autoantibodies in confirmed CJD patients, raising questions about their significance. We performed a scoping review of published CJD cases with co-occurring antibodies, including antineuronal (e.g., NMDAR, LGI1, CASPR2, VGKC, GAD65, GlyR), anti-thyroid peroxidase, antinuclear, and infection-related antibodies, to characterize patient demographics, clinical and diagnostic features, and outcomes, and explore the pathophysiological implications of this association.

Methods

We searched PubMed and Scopus databases up to June 2024, following a published protocol. We included definite/probable CJD cases in which serum/CSF testing detected autoantibodies. Demographic information, clinical presentations, diagnostic findings, treatments, and outcomes were analyzed.

Results

We identified 65 CJD patients with co-occurring antibodies and reported an additional case of a 58-year-old woman with genetic CJD and co-existing anti-TPO and weakly positive CASPR2 antibodies. The median age was 61 years (range 28–82), with NMDAR-Ab patients older and LGI1/CASPR2-Ab cases younger. Most were diagnosed with sporadic CJD (86%) and confirmed by CJD biomarkers (RT-QuIC 100%, 14–3-3 92.6%, Tau 91.7%). Antibodies were mainly found in serum (87.2% vs. 29.8% in CSF). Rapidly progressive dementia was universal, with gait impairment (71.9%) and movement disorders (59.4%) being common. Most cases showed no improvement with immunotherapy, indicating that antibodies may be an epiphenomenon. However, a few cases had transient or partial improvement, suggesting a possible modulatory role or dual pathology.

Conclusion

Antibodies are increasingly noted in CJD as a secondary effect of neurodegeneration. They complicate diagnosis and rarely suggest treatable aspects of the disease. More research is needed to clarify their complex role.

背景：克雅氏病（Creutzfeldt-Jakob disease， CJD）是一种罕见的、进展迅速的朊病毒性神经退行性疾病，可导致致死性痴呆。最近，有报道在确诊的克雅氏病患者中发现了各种自身抗体，对其意义提出了疑问。我们对已发表的CJD共发生抗体的病例进行了范围综述，包括抗神经元抗体（如NMDAR、LGI1、CASPR2、VGKC、GAD65、GlyR）、抗甲状腺过氧化物酶、抗核抗体和感染相关抗体，以表征患者人口统计学特征、临床和诊断特征以及结果，并探讨这种关联的病理生理意义。方法：我们检索PubMed和Scopus数据库，截至2024年6月，遵循已发表的协议。我们纳入了血清/脑脊液检测检测到自身抗体的确诊/疑似CJD病例。分析了人口统计信息、临床表现、诊断结果、治疗方法和结果。结果：我们确定了65例CJD患者同时存在抗体，并报告了另外一例58岁女性遗传性CJD患者同时存在抗tpo和弱阳性CASPR2抗体。中位年龄为61岁（28-82岁），NMDAR-Ab患者年龄较大，LGI1/CASPR2-Ab患者年龄较小。大多数诊断为散发性CJD(86%)，并通过CJD生物标志物（RT-QuIC 100%, 14-3-3 92.6%, Tau 91.7%）确诊。抗体主要存在于血清中（87.2% vs. CSF 29.8%）。快速进展性痴呆是普遍的，步态障碍（71.9%）和运动障碍（59.4%）是常见的。大多数病例显示免疫治疗没有改善，表明抗体可能是一种附带现象。然而，少数病例有短暂或部分改善，提示可能的调节作用或双重病理。结论：抗体作为神经退行性变的继发效应在克雅氏病中越来越受到关注。它们使诊断复杂化，很少提示疾病的可治疗方面。需要更多的研究来阐明它们的复杂作用。

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引用次数: 0

TMEM132A autoimmunity in patients with suspected autoimmune cerebellar ataxia 怀疑自身免疫性小脑性共济失调患者的TMEM132A自身免疫

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-14 DOI: 10.1016/j.jneuroim.2026.578867

Akio Kimura , Akira Takekoshi , Yuri Miyazaki , Kentaro Oh-hashi , Sachiko Kamada , Yukie Taguchi , Masashiro Sugawara , Tsubasa Watanabe , Yuji Ueno , Hiroaki Yaguchi , Ichiro Yabe , Yuko Fukata , Masaki Fukata , Takayoshi Shimohata

Autoimmune cerebellar ataxia (ACA) refers to immune-mediated cerebellar ataxia. The autoantibodies involved in ACA can be detected in patients and are important biomarkers. In this study, we aimed to identify a novel autoantibody in patients with ACA. We screened for autoantibodies in serum samples from patients with cerebellar ataxia using immunohistochemical and immunocytochemical assays. Immunoprecipitation and mass spectrometry were used to identify the target antigens of the detected autoantibodies. We found that IgG reacted with transmembrane protein family 132 A (TMEM132A), which is enriched in the central nervous system (CNS), in serum samples of patients with cerebellar ataxia. A cell-based binding assay (CBA) was used to identify TMEM132A-IgG in serum samples obtained from 436 patients with cerebellar ataxia requiring differential diagnosis for ACA, 62 patients with autoimmune encephalitis, 27 patients with multiple system atrophy with predominant cerebellar ataxia, 24 patients with multiple sclerosis, 17 patients with neuromyelitis optica spectrum disorders, 17 patients with Parkinson's disease, 7 patients with anti-myelin oligodendrocyte glycoprotein antibody-associated disease, and 14 healthy subjects. We detected TMEM132A-IgG in serum samples from two patients with cerebellar ataxia, including the patient whose study first led to the identification of this autoantibody. None of the other participants had these autoantibodies. The two autoantibody-positive patients showed progressive predominant cerebellar ataxia with pyramidal tract signs and albuminocytologic dissociation. Brain MRI findings indicated cerebellar atrophy in one patient and bilateral inferior olivary nuclei hyperintensity changes and pseudohypertrophy in the other patient. TMEM132 A-IgG may be a novel autoantibody associated with autoimmune CNS diseases, including ACA.

自身免疫性小脑共济失调（ACA）是指免疫介导的小脑共济失调。ACA相关的自身抗体可以在患者体内检测到，是重要的生物标志物。在这项研究中，我们的目的是在ACA患者中鉴定一种新的自身抗体。我们使用免疫组织化学和免疫细胞化学方法筛选小脑性共济失调患者血清样本中的自身抗体。采用免疫沉淀法和质谱法对检测到的自身抗体的靶抗原进行鉴定。在小脑性共济失调患者的血清样本中，我们发现IgG与富集于中枢神经系统的跨膜蛋白家族132A （TMEM132A）发生反应。采用细胞结合法（CBA）对436例需要鉴别诊断ACA的小脑性共济失调患者、62例自身免疫性脑炎患者、27例多系统萎缩伴特发性小脑性共济失调患者、24例多发性硬化症患者、17例视神经脊髓炎患者、17例帕金森病患者的血清样本进行TMEM132A-IgG的鉴定。抗髓鞘少突胶质细胞糖蛋白抗体相关疾病7例，健康对照14例。我们在两名小脑性共济失调患者的血清样本中检测到TMEM132A-IgG，其中包括在研究中首次鉴定出这种自身抗体的患者。其他参与者都没有这些自身抗体。两例自身抗体阳性患者表现为进行性占优势的小脑性共济失调，伴有锥体束征象和白蛋白细胞分离。脑MRI显示一名患者小脑萎缩，另一名患者双侧下橄榄核高强度改变和假性肥大。TMEM132 a - igg可能是一种与自身免疫性中枢神经系统疾病（包括ACA）相关的新型自身抗体。

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引用次数: 0

Exercise ameliorates microglial activation and cognitive impairment induced by GFAT1 knockdown after traumatic brain injury 运动可改善创伤性脑损伤后GFAT1敲低引起的小胶质细胞激活和认知障碍

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-13 DOI: 10.1016/j.jneuroim.2026.578868

Tianyu Zai , Mengqi Liu , Weiguan Chen , Chengwei Duan , Jiahao Zhang , Baohao Zheng , Hongjian Lu

Background

The potential of exercise to prevent traumatic brain injury (TBI) has been extensively studied. Microglia play a critical role in TBI pathogenesis. Glutamine-fructose-6-phosphate transaminase 1 (GFAT1), the key enzyme regulating the hexosamine biosynthetic pathway (HBP), not only controls glucose influx but also plays an important role in the neuroinflammatory process. However, the relationship between GFAT1 expression and microglial metabolic activity during treadmill exercise in TBI mice remains unclear.

Methods

A mouse TBI model was established via needle puncture, with mice randomly divided into sedentary and 14-day voluntary treadmill-running exercise groups. GFAT1 knockdown was achieved using GFAT1 shRNA lentivirus. Behavioral tests, electrophysiological recordings, immunohistochemistry, immunofluorescence, and Western blotting evaluated microglial activation and neurological function. An in vitro cell model was constructed with irisin and LPS, using Western blotting and TUNEL staining to assess inflammatory proteins and neuronal apoptosis.

Results

The TBI group showed higher GFAT1 expression than the sham group. Following TBI induction, GFAT1 knockdown increased Interleukin-6(IL-6) expression and aggravate cognitive impairment. While exercise training promoted cognitive function recovery, reduced IL-6 expression, and upregulated the expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In vitro LPS stimulation induced the expression of GFAT1, IL-6, and iNOS; however, GFAT1 knockdown further exacerbated the expression of IL-6 and iNOS. Furthermore, irisin pretreatment led to a reduction in neuronal apoptosis, an increase in Nrf2 and HO-1 expression, and a decrease in IL-6 and iNOS expression.

Conclusion

Exercise ameliorates microglial activation and cognitive impairment induced by GFAT1 knockdown after traumatic brain injury.

运动预防创伤性脑损伤（TBI）的潜力已经得到了广泛的研究。小胶质细胞在TBI发病中起关键作用。谷氨酰胺-果糖-6-磷酸转氨酶1 （GFAT1）是调节己糖胺生物合成途径（HBP）的关键酶，不仅控制葡萄糖内流，而且在神经炎症过程中发挥重要作用。然而，GFAT1表达与TBI小鼠在跑步机运动中小胶质细胞代谢活性之间的关系尚不清楚。方法采用针刺法建立小鼠脑损伤模型，将小鼠随机分为久坐组和14 d自愿跑步组。利用GFAT1 shRNA慢病毒实现了GFAT1的敲除。行为测试、电生理记录、免疫组织化学、免疫荧光和Western blotting评估小胶质细胞激活和神经功能。用鸢尾素和LPS构建体外细胞模型，采用Western blotting和TUNEL染色检测炎症蛋白和神经元凋亡。结果脑外伤组GFAT1表达明显高于假手术组。TBI诱导后，GFAT1敲低可增加白细胞介素-6（IL-6）的表达，加重认知障碍。运动训练促进认知功能恢复，降低IL-6表达，上调核因子e2相关因子2 （Nrf2）和血红素加氧酶-1 （HO-1）表达。体外LPS刺激诱导GFAT1、IL-6和iNOS的表达；而GFAT1敲低进一步加剧了IL-6和iNOS的表达。此外，鸢尾素预处理导致神经元凋亡减少，Nrf2和HO-1表达增加，IL-6和iNOS表达降低。结论运动可改善创伤性脑损伤后GFAT1敲低引起的小胶质细胞活化和认知功能障碍。

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引用次数: 0

Effect on disease activity of ofatumumab in the treatment of glial fibrillary acidic protein astrocytopathy and 18F-DPA714 PET/MRI imaging assessment ofatumumab治疗胶质纤维酸性蛋白星形细胞病对疾病活动性的影响及18F-DPA714 PET/MRI成像评估

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-12 DOI: 10.1016/j.jneuroim.2026.578862

Yingbo Han , Xiaoyu Chen , Qinming Zhou , Ruifen Duan , Mengmeng Zhang , Sheng Chen , Huanyu Meng

A 49-year-old male with Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A) presented with progressive cognitive decline, visual hallucinations, and bowel/bladder incontinence. Brain MRI revealed extensive white matter hyperintensities on T2-FLAIR sequences. After suboptimal response to first-line treatments including corticosteroids and intravenous immunoglobulin (IVIg), the patient was initiated on Ofatumumab (OFA) therapy. Treatment response was systematically monitored through validated clinical assessment tools (MMSE, MoCA, mRS, and CASE) and advanced neuroimaging, including conventional MRI and ¹⁸F-DPA714 PET. Following OFA treatment, the patient demonstrated marked clinical improvement and radiological resolution. Notably, ¹⁸F-DPA714 PET imaging captured dynamic changes in neuroinflammation and revealed distinct patterns not apparent on conventional MRI. This case demonstrates the potential effect on disease activity and safety of OFA in GFAP-A treatment while highlighting the value of ¹⁸F-DPA714 PET as an innovative tool for monitoring neuroinflammation and therapeutic response. To our knowledge, this represents the first comprehensive multimodal assessment using ¹⁸F-DPA714 PET/MRI in a GFAP-A patient treated with ofatumumab.

一位49岁男性胶质纤维酸性蛋白星形细胞病（gmap -A）表现为进行性认知能力下降，视觉幻觉和肠/膀胱失禁。脑MRI在T2-FLAIR序列上显示广泛的白质高信号。在对包括皮质类固醇和静脉注射免疫球蛋白（IVIg）在内的一线治疗反应不佳后，患者开始接受Ofatumumab （OFA）治疗。通过有效的临床评估工具（MMSE、MoCA、mRS和CASE）和先进的神经影像学（包括常规MRI和18F-DPA714 PET）系统监测治疗反应。经OFA治疗后，患者表现出明显的临床改善和放射学缓解。值得注意的是，18F-DPA714 PET成像捕获了神经炎症的动态变化，并显示了传统MRI上不明显的独特模式。该病例证明了OFA在gap - a治疗中对疾病活动性和安全性的潜在影响，同时强调了18F-DPA714 PET作为监测神经炎症和治疗反应的创新工具的价值。据我们所知，这是首次在接受ofatumumab治疗的gap - a患者中使用18F-DPA714 PET/MRI进行全面的多模式评估。

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引用次数: 0

Chronic stress, gut dysbiosis, and cholesterol metabolism: Implications for Alzheimer's disease 慢性应激、肠道失调和胆固醇代谢：对阿尔茨海默病的影响

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-06 DOI: 10.1016/j.jneuroim.2026.578853

Ashmita Das , Navya P. , Durlav Chowdhury , Arijit Das , Rahul Manna , Surendra H. Bodakhe

Alzheimer's disease is a degenerative neurological condition that gradually worsens and is the predominant type of dementia evident in millions of individuals globally. The intricate origin and development of this condition includes multiple genetic and environmental risk factors, alterations in gene expression, and activation of detrimental pathways. Chronic stress can adversely affect brain structure and function, leading to diminished cognitive ability, impaired decision-making, and poor mood regulation. The gut-brain axis, influenced by dietary and early life variables, significantly affects the control of stress responses. The human microbiota forms a symbiotic interaction with the host, impacting protective cell barriers, metabolic processes, and immune functions in the intestines. Chronic stress and high-cholesterol diets can alter gut microbiota composition, influencing behaviour, immune responses, and intestinal function. Oxysterols affect gut health and inflammation through the alteration of tight junctions and the stimulation of proinflammatory bacterial proliferation. This review provides a thorough explanation of the structure and function of the dietary stress system, its relationship with the central nervous system (CNS) and endocrine axis, and evidence connecting stress to the core processes of stress-related illnesses impacting AD. A thorough comprehension of the complex interplay among chronic stress, gut dysbiosis, and Alzheimer's disease progression could provide novel insights for the formulation of targeted therapeutic interventions.

阿尔茨海默病是一种逐渐恶化的退行性神经系统疾病，是全球数百万人的主要痴呆症类型。这种情况的复杂起源和发展包括多种遗传和环境风险因素、基因表达的改变和有害途径的激活。慢性压力会对大脑结构和功能产生负面影响，导致认知能力下降、决策能力受损、情绪调节能力差。肠脑轴受饮食和早期生活变量的影响，显著影响应激反应的控制。人类微生物群与宿主形成共生相互作用，影响肠道内的保护性细胞屏障、代谢过程和免疫功能。慢性应激和高胆固醇饮食可改变肠道菌群组成，影响行为、免疫反应和肠道功能。氧化甾醇通过改变紧密连接和刺激促炎细菌增殖来影响肠道健康和炎症。本文综述了饮食应激系统的结构和功能、与中枢神经系统（CNS）和内分泌轴的关系，以及应激与影响AD的应激相关疾病的核心过程有关的证据。全面了解慢性应激、肠道生态失调和阿尔茨海默病进展之间复杂的相互作用，可以为制定有针对性的治疗干预措施提供新的见解。

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引用次数: 0

B cell tolerance checkpoint function in multiple sclerosis and transient CD52 depletion B细胞耐受检查点在多发性硬化症和短暂CD52耗竭中的作用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2026-01-05 DOI: 10.1016/j.jneuroim.2026.578854

Anastasia Alexaki , Fotis Baltoumas , Dimitrios Tzanetakos , Chrysoula Zografou , Theodoros Dame , Chrysoula Michaletou , Galini Kyriakaki , Aglaia G. Vakrakou , Maria Anagnostouli , Georgia Karadima , Marianna Tzanoudaki , Marinos C. Dalakas , Leonidas Stefanis , Konstantinos Kilidireas , Kevin C. O'Connor , Georgios Pavlopoulos , Panos Stathopoulos

Transient CD52 immune cell depletion with the monoclonal antibody alemtuzumab is highly effective in treating relapsing-remitting multiple sclerosis but often leads to secondary autoimmunity. Whether these effects are linked to an alteration of B cell tolerance mechanisms is currently not known. To evaluate peripheral B cell tolerance checkpoint integrity in patients and controls, we constructed 138 recombinant mAbs from single mature naïve B cells and tested their poly- and autoreactivity. We examined three healthy donors (HDs), three immunotherapy-naïve MS patients, and six patients treated with alemtuzumab at comparable time points post-treatment (mean ± SD 3.8 ± 0.39 years). Moreover, we investigated B cell receptor (BCR) repertoire parameters associated with tolerance mechanisms in the same subject groups. Polyreactive and autoreactive fraction means did not differ significantly among the three subgroups. Presence of a high or low autoreactive fraction of naïve B cells in patients treated with alemtuzumab did not correlate with secondary autoimmunity at the time of sampling and with future MS activity, and therefore most likely reflects stochastic variation in the context of immune reconstitution. In BCR repertoire analysis, alemtuzumab-treated patients showed lower mean naïve complementarity-determining region 3 (CDR3) net charge compared to HDs (P = 0.0036), an interesting yet isolated finding warranting further investigation. Overall, transient CD52 depletion did not seem to affect major changes in peripheral B cell tolerance checkpoint function as assessed with naïve B cell cloning and BCR NGS, while observations in the described setting may also apply to other immune reconstitution therapies.

短暂的CD52免疫细胞耗竭与单克隆抗体阿仑妥珠单抗在治疗复发-缓解型多发性硬化方面非常有效，但经常导致继发性自身免疫。这些影响是否与B细胞耐受机制的改变有关目前尚不清楚。为了评估患者和对照组外周B细胞耐受检查点的完整性，我们从单个成熟naïve B细胞中构建了138个重组单克隆抗体，并测试了它们的多反应性和自身反应性。我们在治疗后的可比较时间点（平均±SD 3.8±0.39年）检查了3名健康供体（hd）、3名immunotherapy-naïve MS患者和6名接受阿仑单抗治疗的患者。此外，我们还研究了相同受试者组中与耐受机制相关的B细胞受体（BCR）库参数。多反应性和自反应性分数均值在三个亚组之间无显著差异。在接受阿仑单抗治疗的患者中，naïve B细胞的高或低自身反应部分与采样时的继发性自身免疫和未来的MS活性无关，因此很可能反映了免疫重建背景下的随机变异。在BCR全库分析中，与hd相比，阿仑单抗治疗的患者表现出更低的naïve互补决定区3 （CDR3）平均净电荷（P = 0.0036），这是一个有趣但孤立的发现，值得进一步研究。总体而言，通过naïve B细胞克隆和BCR NGS评估，短暂的CD52耗尽似乎不会影响外周B细胞耐受检查点功能的主要变化，而上述情况的观察结果也可能适用于其他免疫重建疗法。

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引用次数: 0

Mitochondrial dysregulation as a central mechanism in autism spectrum disorder pathogenesis 线粒体失调是自闭症谱系障碍发病的核心机制。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-12-31 DOI: 10.1016/j.jneuroim.2025.578851

Xiaoli Liao , Jingqi Shao , Zhihui Chen

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic predispositions and environmental insults. However, the precise molecular mechanisms linking prenatal environmental perturbations to neurodevelopmental impairments remain poorly defined. This study investigates the role of mitochondrial dysfunction and metabolic disturbances in ASD pathogenesis using various preclinical models, including the maternal immune activation (MIA) and ASD high-risk gene knockout models. We performed transcriptomic profiling on mouse brain tissues to identify differentially expressed genes (DEGs) associated with mitochondrial and metabolic pathways. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed significant disruptions in pathways such as oxidative phosphorylation, tricarboxylic acid, and energy metabolism. These findings point to mitochondrial dysfunction as a central mechanism contributing to metabolic imbalances in ASD. Comparative analysis with publicly available RNA-seq datasets from PTEN knockout model revealed both shared and unique metabolic signatures. Single-cell RNA-seq data from the MIA model further identified cell-type-specific metabolic alterations in distinct neuronal and glial populations. Additionally, analysis of the Human Fetal Single-Cell Atlas highlighted the relevance of these metabolic pathways in human brain development. Collectively, these results emphasize mitochondrial metabolism as a potential therapeutic target for ASD, offering insights into the molecular basis of this disorder.

自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，受遗传易感性和环境损害的影响。然而，将产前环境扰动与神经发育障碍联系起来的精确分子机制仍然不明确。本研究通过多种临床前模型，包括母体免疫激活（MIA）和ASD高危基因敲除模型，探讨线粒体功能障碍和代谢紊乱在ASD发病机制中的作用。我们对小鼠脑组织进行转录组学分析，以鉴定与线粒体和代谢途径相关的差异表达基因（DEGs）。功能富集分析，包括基因本体（GO）和京都基因与基因组百科全书（KEGG），揭示了氧化磷酸化、三羧酸和能量代谢等途径的显著破坏。这些发现表明，线粒体功能障碍是导致ASD代谢失衡的主要机制。与PTEN基因敲除模型的公开RNA-seq数据集进行比较分析，揭示了共享和独特的代谢特征。来自MIA模型的单细胞RNA-seq数据进一步确定了不同神经元和神经胶质群体中细胞类型特异性代谢改变。此外，对人类胎儿单细胞图谱的分析强调了这些代谢途径在人类大脑发育中的相关性。总的来说，这些结果强调线粒体代谢是ASD的潜在治疗靶点，为这种疾病的分子基础提供了见解。

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引用次数: 0

Efficacy and tolerability of metformin as an adjuvant therapy in patients with relapse-remitting multiple sclerosis receiving interferon Beta 1a: A randomized pilot trial 二甲双胍作为辅助治疗接受干扰素β 1a的复发缓解型多发性硬化症患者的疗效和耐受性：一项随机试验

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-12-31 DOI: 10.1016/j.jneuroim.2025.578852

Mohamed Y. Abdelgaied , Omar Abdelgawad , Mohamed Hamed Rashad , Mohamed H. Solayman , Hend M. El-Tayebi

Background

Neurodegeneration and inflammation can accelerate the demyelination process in multiple sclerosis (MS). We aimed to investigate the efficacy and tolerability of metformin as an add-on treatment to interferon Beta 1a (IFNβ-1a) in Egyptian patients with relapsing-remitting multiple sclerosis (RRMS).

Method

Thirty RRMS patients were divided into two groups: the experimental arm receiving IFNβ-1a plus 2 g of metformin once daily and the control arm receiving IFNβ-1a alone. Tolerance to metformin was measured for the intervention group. Following 6 months period, serum neurofilament light chain (sNFL) and nuclear factor Kappa B (NF-κB), T2 lesions in magnetic resonance imaging (MRI), and expanded disability status scale (EDSS) were measured.

Results

There were no statistically significant differences between the two groups in the change in the median (interquartile range) of the blood biomarkers (sNFL; −32.8 (21) vs −32.8 (13.4), p = 0.99) and NF-κB; −64.9 (35.1) vs −61.6 (35.7), p = 0.8, respectively). In clinical outcomes, there was no statistically significant in the mean (standard deviation) change of EDSS (0 vs 0, p = 1). For MRI results, 11 patients had a stationary and regressive course 1 patient had a progressive course in the metformin group vs 6 patients had a stationary and regressive course and 2 had a progressive course in the control group, p = 0.23. All outcomes were measured after 6-month follow-ups. The most common side effects of metformin were diarrhea and abdominal pain without incidence of lactic acidosis.

Conclusion

Receiving metformin as an add-on therapy to IFNβ-1a did not result in a significant improvement in neurodegeneration and inflammation blood biomarkers and clinical outcomes. A high dose of metformin (2 g/day) is safe and well tolerated in patients with MS. Additional studies involving larger populations are necessary to confirm or disprove these findings.

Trial registration

ClinicalTrials.gov ID: NCT06812585

背景：神经变性和炎症可加速多发性硬化症（MS）的脱髓鞘过程。我们的目的是研究二甲双胍作为干扰素β 1a （IFNβ-1a）附加治疗在埃及复发-缓解型多发性硬化症（RRMS）患者中的疗效和耐受性。方法30例RRMS患者分为两组，实验组给予IFNβ-1a + 2 g二甲双胍每日1次，对照组单独给予IFNβ-1a治疗。测量干预组对二甲双胍的耐受性。随访6个月，检测血清神经丝轻链（sNFL）、核因子κB （NF-κB）、磁共振成像（MRI） T2病变、扩展残疾状态量表（EDSS）。结果两组患者血液生物标志物(sNFL: - 32.8 （21) vs - 32.8 (13.4), p = 0.99）和NF-κB的中位数（四分位数范围）变化差异无统计学意义；61.6 vs−−64.9(35.1)(35.7),分别为p = 0.8)。在临床结局方面，EDSS的平均（标准差）变化无统计学意义（0 vs 0, p = 1）。MRI结果显示，二甲双胍组11例患者病程平稳消退，1例进展，对照组6例患者病程平稳消退，2例进展，p = 0.23。所有结果在6个月的随访后测量。二甲双胍最常见的副作用是腹泻和腹痛，无乳酸性酸中毒的发生。结论接受二甲双胍作为IFNβ-1a的附加治疗并未导致神经变性和炎症血液生物标志物以及临床结果的显着改善。高剂量二甲双胍（2g /天）对ms患者是安全且耐受性良好的，需要更多的涉及更大人群的研究来证实或反驳这些发现。临床试验注册。gov ID: NCT06812585

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引用次数: 0

Neuroinflammation and metabolic dysfunction drive nerve conduction deficits in diabetic neuropathy: Clinical and in silico insights 神经炎症和代谢功能障碍驱动糖尿病神经病变的神经传导缺陷：临床和计算机观察。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-12-26 DOI: 10.1016/j.jneuroim.2025.578849

Faaz Bin Razi , Sangeeta Singhal , Hamid Ashraf , Shagufta Moin

Diabetic neuropathy is a debilitating complication of type 2 diabetes mellitus (T2DM), largely driven by systemic inflammation and metabolic disturbances. This cross-sectional study assessed the relationship between interleukin-6 (IL-6), vitamin B12, lipid profile, and nerve conduction parameters in T2DM patients with and without neuropathy. Sixty participants were divided evenly into two groups: T2DM without neuropathy (control) and T2DM with confirmed neuropathy (case). Biochemical parameters measured included fasting and postprandial glucose, glycated hemoglobin (HbA1c), vitamin B12, IL-6, renal function, and detailed lipid profiling. Nerve conduction studies assessed sensory and motor nerves in upper and lower limbs. The neuropathy group showed higher IL-6 levels, lower vitamin B12 concentrations, and an atherogenic lipid profile characterised by increased triglycerides, VLDL, and non-HDL cholesterol. Marked reductions in nerve conduction velocities were evident in both sensory and motor nerves, especially in the common peroneal and posterior tibial nerves, which had high diagnostic accuracy with AUC values of 0.88 and 0.84, respectively. Univariate regression identified IL-6 as significantly associated with decreased conduction velocity in radial sensory and posterior tibial nerves. Supporting these clinical findings, in silico pathway enrichment analyses highlighted key roles for IL-6 signalling, vitamin B12 metabolism, lipid pathways, and myelination in diabetic neuropathy pathogenesis. These integrated data underscore inflammation and metabolic dysfunction as pivotal drivers, with IL-6 and nerve conduction studies serving as promising early biomarkers and therapeutic targets.

糖尿病性神经病变是2型糖尿病（T2DM）的一种衰弱性并发症，主要由全身性炎症和代谢紊乱引起。本横断面研究评估了伴有和不伴有神经病变的T2DM患者中白细胞介素-6 （IL-6）、维生素B12、血脂和神经传导参数之间的关系。60名参与者被平均分为两组：无神经病变的T2DM（对照组）和确诊神经病变的T2DM（病例）。测量的生化参数包括空腹和餐后血糖、糖化血红蛋白（HbA1c）、维生素B12、IL-6、肾功能和详细的脂质谱。神经传导研究评估了上肢和下肢的感觉神经和运动神经。神经病变组表现出较高的IL-6水平，较低的维生素B12浓度，以及以甘油三酯、VLDL和非高密度脂蛋白胆固醇升高为特征的动脉粥样硬化性脂质谱。感觉神经和运动神经的神经传导速度均明显降低，尤其是腓总神经和胫后神经，其诊断准确率较高，AUC分别为0.88和0.84。单因素回归发现IL-6与桡侧感觉神经和胫后神经传导速度降低显著相关。支持这些临床发现，硅途径富集分析强调了IL-6信号，维生素B12代谢，脂质途径和髓鞘形成在糖尿病神经病变发病机制中的关键作用。这些综合数据强调炎症和代谢功能障碍是关键驱动因素，IL-6和神经传导研究可作为有希望的早期生物标志物和治疗靶点。

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引用次数: 0

Immature ovarian teratomas in anti-NMDA receptor encephalitis 抗nmda受体脑炎的未成熟卵巢畸胎瘤。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-12-26 DOI: 10.1016/j.jneuroim.2025.578850

Kristen Simone , Nabeela Nathoo , Allyssa Hooper , Albert Aboseif , Andrew Blake Buletko , Niranjala Satkunam , Jennifer A. McCombe , Sophia Pin

Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR-AIE) is an immune-mediated neurological disease with manifestations including altered mental status, neuropsychiatric disturbance, movement disorders, seizure, and dysautonomia. NMDAR-AIE is associated with ovarian teratoma in half of cases, typically mature teratoma. NMDAR-AIE is rarely associated with immature ovarian teratomas. Here, we describe three cases of NMDAR-AIE associated with immature ovarian teratomas. We review diagnosis and management of immature ovarian teratomas in NMDAR-AIE as a collaboration between gynecology and neurology, with multi-disciplinary recommendations provided regarding workup and management.

抗n -甲基-d-天冬氨酸受体自身免疫性脑炎（NMDAR-AIE）是一种免疫介导的神经系统疾病，其表现包括精神状态改变、神经精神障碍、运动障碍、癫痫发作和自主神经异常。NMDAR-AIE在一半的病例中与卵巢畸胎瘤有关，典型的是成熟畸胎瘤。NMDAR-AIE很少与未成熟卵巢畸胎瘤相关。在这里，我们描述了三例与未成熟卵巢畸胎瘤相关的NMDAR-AIE。我们回顾了NMDAR-AIE中未成熟卵巢畸胎瘤的诊断和治疗，作为妇科和神经病学的合作，并提供了关于检查和治疗的多学科建议。

引用次数: 0