Journal of neuroimmunology最新文献

{"title":"Postbiotics and the gut–brain axis: A mechanistic review on modulating neuroinflammation and cognitive aging","authors":"Rijhul Lahariya ,&nbsp;Gargee Anand ,&nbsp;Bandana Kumari ,&nbsp;Ketan Priyadarshi","doi":"10.1016/j.jneuroim.2026.578870","DOIUrl":"10.1016/j.jneuroim.2026.578870","url":null,"abstract":"<div><div>Aging triggers gut microbiota dysbiosis that disrupts the gut-brain axis (GBA), promoting neuroinflammation and neurodegeneration. Elderly exhibit reduced microbial diversity, depleted beneficial bacteria, and expanded pathobionts, elevating neurotoxic metabolites—lipopolysaccharides (LPS), trimethylamine-N-oxide, kynurenine derivatives, and secondary bile acids. These drive “inflammaging,” blood-brain barrier breakdown, microglial activation, mitochondrial impairment, and proteinopathies in Alzheimer's and Parkinson's disease. Conversely, neuroprotective metabolites from commensals—short-chain fatty acids, indole-3-propionic acid, and urolithins—preserve gut integrity, suppress inflammation, upregulate BDNF for synaptic plasticity, and enhance mitophagy. Postbiotics, stable probiotic-derived bioactives (butyrate, polyphenol metabolites, and lactate derivatives), surpass live probiotics in safety and precision. They modulate GBA via histone deacetylase inhibition, GPR41/43 signaling, NF-κB blockade, and microglial M2 shift, blocking LPS translocation and bolstering neuronal resilience. Preclinical rodent studies demonstrate robust neuroprotection, but human translation reveals challenges: inter-individual microbiota variability (diet/genetics/comorbidities), inconsistent metabolite absorption/brain penetration between species, methodological limitations (16S rRNA vs. functional metagenomics), postbiotic standardization barriers, and sparse Phase I/II trials showing biomarker benefits without cognitive endpoints. This review synthesizes gut dysbiosis-metabolite-brain aging mechanisms, positioning postbiotics as precision therapeutics. Multi-omics stratified controlled trials are essential to validate long-term efficacy for delaying neurodegeneration and extending cognitive health.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578870"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030138","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}

{"title":"Serum from patients with acetylcholine receptor antibody–positive myasthenia gravis triggers pathogenic changes in human myotube cells","authors":"Keisuke Tanaka ,&nbsp;Akiyuki Uzawa ,&nbsp;Manato Yasuda ,&nbsp;Yosuke Onishi ,&nbsp;Hiroyuki Akamine ,&nbsp;Hideo Handa ,&nbsp;Etsuko Ogaya ,&nbsp;Shota Miyake ,&nbsp;Masayuki Baba ,&nbsp;Hiroto Abe ,&nbsp;Koki Nagaoka ,&nbsp;Yuko Nakatake-Furuie ,&nbsp;Kenichi Serizawa ,&nbsp;Satoshi Kuwabara","doi":"10.1016/j.jneuroim.2026.578871","DOIUrl":"10.1016/j.jneuroim.2026.578871","url":null,"abstract":"<div><h3>Background</h3><div>Some patients with myasthenia gravis (MG) are refractory to available treatments, highlighting the need to further understand the pathogenesis of the disease. This study aimed to determine whether components in the serum from patients with acetylcholine receptor (AChR) antibody–positive MG affect myotubes, to explore their possible role in disease pathogenesis beyond the inhibition of acetylcholine signal transmission.</div></div><div><h3>Methods</h3><div>Serum was collected from 14 patients with AChR antibody–positive MG. The differentiated human myotubes were stimulated with 10% serum from healthy controls or patients with MG. After 24 h, ribonucleic acid extraction/sequencing was performed, and differentially expressed genes (DEGs) were extracted. Pathway analysis was completed using DEGs that were downregulated by stimulation with serum from patients with MG. Expression of genes important for muscle contraction was measured and myotube diameter was determined by immunostaining.</div></div><div><h3>Results</h3><div>Approximately 1200 DEGs were extracted by comparing gene expression in cultured human myotube cells stimulated with serum from healthy controls and patients with MG. Gene ontology terms linked with muscle function were suppressed in myotube cells stimulated with patient serum. Suppression of pathways associated with muscle atrophy/weakness, decreased expression of genes associated with muscle contraction, and smaller myotube diameter were confirmed in myotube cells stimulated with serum from patients versus healthy controls.</div></div><div><h3>Conclusion</h3><div>Factors other than acetylcholine signal transmission inhibition may contribute to the pathogenesis of AChR antibody–positive MG. Further research is needed to clarify the pathways involved, potentially leading to more tailored pharmacotherapies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578871"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079052","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}

{"title":"Chronic stress, gut dysbiosis, and cholesterol metabolism: Implications for Alzheimer's disease","authors":"Ashmita Das ,&nbsp;Navya P. ,&nbsp;Durlav Chowdhury ,&nbsp;Arijit Das ,&nbsp;Rahul Manna ,&nbsp;Surendra H. Bodakhe","doi":"10.1016/j.jneuroim.2026.578853","DOIUrl":"10.1016/j.jneuroim.2026.578853","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578853"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929195","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}

{"title":"Free light chains analysis in cerebrospinal fluid for the diagnosis of multiple sclerosis: A study in the Israeli population","authors":"Alina Ostrovsky,&nbsp;Amos J. Simon,&nbsp;Batia Kaplan","doi":"10.1016/j.jneuroim.2026.578873","DOIUrl":"10.1016/j.jneuroim.2026.578873","url":null,"abstract":"<div><h3>Background</h3><div>The 2024 revision of the McDonald criteria for multiple sclerosis (MS) recognized kappa free light chain (FLCκ) as a quantitative biomarker of intrathecal immunoglobulin synthesis equivalent to oligoclonal bands (OCB). However, diagnostic performance of reported FLC thresholds vary across laboratories due to differences in instrumentation, assay type, population and regional characteristics.</div></div><div><h3>Objectives</h3><div>Assessing of the utility of nephelometric FLC assay for MS diagnosis in an Israeli cohort.</div></div><div><h3>Methods</h3><div>A total of 135 patients with MS, non-MS demyelinating/inflammatory and non-demyelinating neurological disorders were tested using FLC assay and OCB technique. FLCκ and λ concentration and their index values were estimated. Statistical analysis methods included Mann-Whitney and Kruskal-Wallis tests, Spearman correlation, and receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>FLCκ metrics outperformed FLCλ in diagnosing MS. Using FLCκ index, a threshold 7.0 yielded 82% specificity and 77.1% sensitivity, while 72% specificity and 82% sensitivity was achieved using κ concentration cut-off 0.19 mg/L. Specificity of OCB test (84%) was similar to that of FLCκ index, though OCB sensitivity (88.6%) exceeded the FLC-based metrics. Specifically, cases with κ index &gt;11 and concentration &gt; 0.2 mg/L were MS or OCB-positive, whereas cases with κ concentration &lt; 0.1 mg/L were non-MS or OCB-negative. Hence, 60% of the cases may be safely excluded from OCB testing.</div></div><div><h3>Conclusions</h3><div>Optimized FLCκ thresholds effectively assist MS diagnosis within Israeli population. Combined FLC thresholds (κ index and concentration values) were established for screening clearly defined/unequivocal cases that may not require time-consuming operator-dependent OCB analysis. Rapid quantitative FLC assay holds promise as a screening tool for unequivocal cases prior to OCB testing.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578873"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078898","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}

{"title":"Effect on disease activity of ofatumumab in the treatment of glial fibrillary acidic protein astrocytopathy and 18F-DPA714 PET/MRI imaging assessment","authors":"Yingbo Han ,&nbsp;Xiaoyu Chen ,&nbsp;Qinming Zhou ,&nbsp;Ruifen Duan ,&nbsp;Mengmeng Zhang ,&nbsp;Sheng Chen ,&nbsp;Huanyu Meng","doi":"10.1016/j.jneuroim.2026.578862","DOIUrl":"10.1016/j.jneuroim.2026.578862","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578862"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980837","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}

{"title":"B cell tolerance checkpoint function in multiple sclerosis and transient CD52 depletion","authors":"Anastasia Alexaki ,&nbsp;Fotis Baltoumas ,&nbsp;Dimitrios Tzanetakos ,&nbsp;Chrysoula Zografou ,&nbsp;Theodoros Dame ,&nbsp;Chrysoula Michaletou ,&nbsp;Galini Kyriakaki ,&nbsp;Aglaia G. Vakrakou ,&nbsp;Maria Anagnostouli ,&nbsp;Georgia Karadima ,&nbsp;Marianna Tzanoudaki ,&nbsp;Marinos C. Dalakas ,&nbsp;Leonidas Stefanis ,&nbsp;Konstantinos Kilidireas ,&nbsp;Kevin C. O'Connor ,&nbsp;Georgios Pavlopoulos ,&nbsp;Panos Stathopoulos","doi":"10.1016/j.jneuroim.2026.578854","DOIUrl":"10.1016/j.jneuroim.2026.578854","url":null,"abstract":"<div><div>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 (<em>P</em> = 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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578854"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908897","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}

{"title":"The NEDD8-activating enzyme inhibitor MLN4924 reduces inflammation, blood-brain barrier disruption and brain injury after intracerebral hemorrhage in mice","authors":"Yu Huang ,&nbsp;Zihan Wang ,&nbsp;Shaochen Wang ,&nbsp;Chenxi Liu ,&nbsp;Luping Chang ,&nbsp;Xue Geng ,&nbsp;Pengyue Du ,&nbsp;Yong-Chen Wang ,&nbsp;Wenying Fan ,&nbsp;Bing-Qiao Zhao","doi":"10.1016/j.jneuroim.2026.578872","DOIUrl":"10.1016/j.jneuroim.2026.578872","url":null,"abstract":"<div><div>Inflammation is a key factor leading to secondary brain injury after intracerebral hemorrhage (ICH). Neddylation, a post-translational modification that attaches NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) to targets, regulates diverse cellular processes. Neddylation is overactivated in various cancers and linked to atherosclerosis and inflammatory disorders, but its role in ICH remains unclear. In this study, mice were subjected to ICH by injection of collagenase. The NEDD8-activating enzyme inhibitor MLN4924 was administered subcutaneously post-ICH. We found that NEDD8 expression was upregulated in macrophages and microglia after ICH. Treatment with MLN4924 reduced NEDD8 expression, cullin-1 neddylation, macrophage infiltration, microglial activation, and the production of proinflammatory cytokines. These anti-inflammatory effects were accompanied by attenuated loss of tight junction proteins, blood-brain barrier (BBB) damage, neuronal degeneration and brain injury, and improved neurological function. Furthermore, MLN4924 treatment induced the accumulation of the cullin-RING E3 ligase substrates, including phosphorylated ERK5 and KLF2, and reduced ICAM-1 expression. Inhibiting ERK5 reversed the beneficial effects of MLN4924 on inflammation, BBB disruption, and neurobehavioral deficits. Collectively, inhibition of the NEDD8 pathway by MLN4924 attenuates inflammation, BBB disruption, and neurological deficits via the p-ERK5-KLF2-ICAM-1 axis, highlighting NEDD8 pathway as a potential therapeutic target for ICH.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578872"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078948","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}

{"title":"Exosomes derived from neural stem cells contribute to cerebral ischemia/reperfusion injury via inhibiting autophagy in rats","authors":"Li Xiong ,&nbsp;Siying Huo ,&nbsp;Yuan Yang ,&nbsp;Qi Zhang ,&nbsp;Junjie Li ,&nbsp;Wenya Bai ,&nbsp;Jia Liu ,&nbsp;Jianlin Shao","doi":"10.1016/j.jneuroim.2026.578875","DOIUrl":"10.1016/j.jneuroim.2026.578875","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia-reperfusion injury (CIRI) represents a critical pathological mechanism underlying stroke. Exosomes (EXOs) are biological vesicles released by cells, containing active components and functional properties of their cell of origin. This study investigates the impact of human neural stem cell-derived exosomes (hNSC-EXOs) on the CIRI rat model, focusing on neuronal autophagy, and provides a novel theoretical foundation for future clinical interventions in CIRI management.</div></div><div><h3>Methods</h3><div>PKH26-labeled hNSC-EXOs were traced in vivo and in vitro. After establishing CIRI model, hNSC-EXOs were administered for treatment. Brain injury and variations in inflammatory factors were compared at 24 h after operation. The impact of hNSC-EXOs on neuronal autophagy was examined by detecting the expression of Beclin-1, Atg-5, and LC3B, and observing the changes in the number of autophagosomes using TEM of the right cerebral cortex of rats.</div></div><div><h3>Results</h3><div>The average particle size and concentration of hNSC-EXO were 64.47 nm and 8.96 × 10¹⁰/ml, respectively. PKH26-labeled hNSC-EXOs was taken up by BV2 and HT22 cells, and was mainly located in the brain injury area in vivo, with their total flux showing a time-dependent characteristic. hNSC-EXO treatment reduced the neurological score, cerebral infarct volume, and cerebral edema in the CIRI model. Brain tissue staining showed that hNSC-EXO attenuated Nissl body damage and neuronal apoptosis in the CIRI model. Regarding inflammatory factors, hNSC-EXO increased serum levels of IL-4 and IL-10, and decreased levels of TNF-α, iNOS, and IL-6 in the CIRI model. Notably, hNSC-EXO reduced the expression of Beclin-1, Atg-5, and LC3 and the number of autophagosomes in the brain tissue of the CIRI model.</div></div><div><h3>Conclusion</h3><div>hNSC-EXOs exert an antagonistic effect with CIRI, effectively inhibiting excessive neuronal autophagy, reducing the inflammatory response and neuronal apoptosis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578875"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079049","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}

{"title":"TMEM132A autoimmunity in patients with suspected autoimmune cerebellar ataxia","authors":"Akio Kimura ,&nbsp;Akira Takekoshi ,&nbsp;Yuri Miyazaki ,&nbsp;Kentaro Oh-hashi ,&nbsp;Sachiko Kamada ,&nbsp;Yukie Taguchi ,&nbsp;Masashiro Sugawara ,&nbsp;Tsubasa Watanabe ,&nbsp;Yuji Ueno ,&nbsp;Hiroaki Yaguchi ,&nbsp;Ichiro Yabe ,&nbsp;Yuko Fukata ,&nbsp;Masaki Fukata ,&nbsp;Takayoshi Shimohata","doi":"10.1016/j.jneuroim.2026.578867","DOIUrl":"10.1016/j.jneuroim.2026.578867","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578867"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018859","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}

{"title":"Neuroinflammation and metabolic dysfunction drive nerve conduction deficits in diabetic neuropathy: Clinical and in silico insights","authors":"Faaz Bin Razi ,&nbsp;Sangeeta Singhal ,&nbsp;Hamid Ashraf ,&nbsp;Shagufta Moin","doi":"10.1016/j.jneuroim.2025.578849","DOIUrl":"10.1016/j.jneuroim.2025.578849","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578849"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849488","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}