Journal of neuroimmunology最新文献

{"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":"2025-12-15","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}

{"title":"Immunity in Parkinson's disease - the role of adaptive and auto-immune responses and gut-microbiome axis","authors":"A.R. Satvik Iyengar ,&nbsp;Peter R. Dunkley,&nbsp;Phillip W. Dickson","doi":"10.1016/j.jneuroim.2025.578755","DOIUrl":"10.1016/j.jneuroim.2025.578755","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by loss of dopaminergic neurons in the mid-brain and accumulation of α-synuclein aggregates referred to as Lewy bodies. PD is a progressive disease and the treatments available are aimed at addressing only its symptomatology. Immune dysregulation is one of the several mechanisms that are hypothesized to contribute towards PD pathogenesis. This review firstly addresses the interaction of innate and adaptive immune components and the role of adaptive immune responses, with a particular focus on T lymphocytes in PD. The review secondly examines the evidence for the involvement of the autoimmune system in PD, including the presence of autoantibodies and the association of autoimmunity with proteins linked with PD (α-synuclein and neuromelanin) and with infections. The review thirdly explores the connection between the gut microbiota the immune system and the impact of this relationship on the pathogenic processes of PD. Finally, this review discusses adaptive immunity based therapeutic strategies for PD, probable PD detection approaches based on autoimmunity, and the potential of gut-microbiome replenishment in PD treatment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578755"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047032","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":"Cerebral amyloid angiopathy-related inflammation superimposed on alpha-synucleinopathies: a case report and literature review","authors":"Mattia Losa ,&nbsp;Francesco Calizzano ,&nbsp;Stefano Grisanti ,&nbsp;Alberto Coccia ,&nbsp;Margherita Bellucci ,&nbsp;Andrea Donniaquio ,&nbsp;Arnoldo Piccardo ,&nbsp;Tiziana Tassinari","doi":"10.1016/j.jneuroim.2025.578783","DOIUrl":"10.1016/j.jneuroim.2025.578783","url":null,"abstract":"<div><h3>Introduction</h3><div>Cerebral amyloid angiopathy-related inflammation (CAAri) is a rare CAA variant characterized by an autoinflammatory response against beta-amyloid and subacute neurological presentation. While biologically plausible, given the frequent co-presence of beta-amyloidosis in synucleinopathies, no documented cases of CAAri superimposed on a dementia with Lewy bodies (DLB) have been previously described.</div></div><div><h3>Methods</h3><div>We presented a case of prodromal DLB, which subsequently manifested a clinical and radiological syndrome consistent with a CAAri. A literature review on case reports of CAAri overlapping with synucleinopathies was performed.</div></div><div><h3>Results</h3><div>The patient met the criteria for prodromal DLB several months earlier and presented with a rapidly progressive cognitive decline. During the diagnostic work-up, a brain MRI revealed disseminated cortical superficial siderosis, multiple lobar microbleeds, and asymmetric confluent areas of vasogenic edema, consistent with a probable CAAri. Corticosteroids were administered based on the suspected diagnosis, resulting in prompt clinical and radiologic improvement.</div></div><div><h3>Conclusions</h3><div>As highlighted in this case, CAAri could be a potential explanation for subacute exacerbations in synucleinopathies (especially in DLB patients), due to the highly prevalent comorbid beta-amyloidosis. This case also emphasizes the need to consider a possible immune-mediated mechanism of neurological deterioration in DLB, especially given its amenability to treatment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578783"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362977","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":"Role of antibodies in immune checkpoint inhibitor–related CNS toxicities: insights from challenging clinical cases","authors":"Jeanne Benoit ,&nbsp;Bastien Joubert ,&nbsp;Alberto Vogrig","doi":"10.1016/j.jneuroim.2025.578778","DOIUrl":"10.1016/j.jneuroim.2025.578778","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment yet are increasingly associated with neurological immune-related adverse events (n-irAEs), which can affect any part of the nervous system. Accurate diagnosis is often challenging due to overlapping features with classical paraneoplastic neurological syndromes (PNS) and autoimmune encephalitis (AE). They may also resemble other neurological conditions, including demyelinating diseases. In this review, we present four illustrative cases of post-ICI n-irAEs involving the central nervous system (CNS). Through these cases and accompanying commentaries providing a critical appraisal of the current literature, we highlight the diagnostic, therapeutic, and prognostic challenges associated with these presentations. We emphasize both the role and limitations of neuronal antibody testing. This review stresses the need for rigorous clinical phenotyping, comprehensive immunological screening, and multidisciplinary management to improve early recognition of these complex and often severe complications and guide future therapeutic strategies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578778"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267858","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":"Mononuclear phagocytes in blood and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis: Untreated and treated with anti-CD20 therapy","authors":"Marie Mathilde Hansen ,&nbsp;Sahla El Mahdaoui ,&nbsp;Malene Bredahl Hansen ,&nbsp;Victoria Hyslop Hvalkof ,&nbsp;Mie Reith Mahler ,&nbsp;Signe Refstrup Husted ,&nbsp;Helle Bach Søndergaard ,&nbsp;Poul Jennum ,&nbsp;Jeppe Romme Christensen ,&nbsp;Marina Rode von Essen ,&nbsp;Finn Sellebjerg","doi":"10.1016/j.jneuroim.2025.578751","DOIUrl":"10.1016/j.jneuroim.2025.578751","url":null,"abstract":"<div><h3>Background</h3><div>Mononuclear phagocytes, including monocytes, macrophages, and microglia, play key roles in the immunopathogenesis of multiple sclerosis (MS). While anti-CD20 monoclonal antibody therapies effectively treat relapsing-remitting MS (RRMS), their secondary effects on mononuclear phagocytes remain unclear.</div></div><div><h3>Objective and methods</h3><div>We analyzed blood and cerebrospinal fluid (CSF) mononuclear phagocytes in patients with RRMS treated with anti-CD20 therapy for 6 months, untreated patients, and controls. Flow cytometry was used to assess the prevalence, phenotype, and cytokine production by blood monocytes. Chitinase-1 (CHIT1) levels in CSF were measured using an enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Blood monocyte frequencies were elevated in untreated and anti-CD20-treated RRMS patients compared with controls. CSF mononuclear phagocytes differed from blood monocytes and were classified as either CD16⁺ or CD16⁻, with CD16⁺ mononuclear phagocytes being enriched in all groups. However, the frequencies of CD16⁻ mononuclear phagocytes in CSF were higher in untreated and anti-CD20-treated RRMS patients compared to controls, and the expression of CD206 and CCR2 on CD16⁻ mononuclear phagocytes differed between untreated patients and controls. Blood monocyte cytokine production did not differ between untreated and anti-CD20-treated patients. CSF CHIT1 levels were elevated in both untreated and anti-CD20-treated patients.</div></div><div><h3>Conclusions</h3><div>The comparable blood and CSF mononuclear phagocyte phenotypes, along with persistently elevated CHIT1 concentrations in CSF of untreated and anti-CD20-treated patients with RRMS, suggest that residual innate immune activation is not normalized by 6 months of anti-CD20 treatment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578751"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047034","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":"Association of thyroid autoimmune status with Alzheimer’s disease biomarkers in euthyroid subjects","authors":"Feifei Ge ,&nbsp;Bo Song ,&nbsp;Xixi Wang ,&nbsp;Minjie Tian ,&nbsp;Xingjian Lin ,&nbsp;Jingping Shi ,&nbsp;Xing Ye","doi":"10.1016/j.jneuroim.2025.578780","DOIUrl":"10.1016/j.jneuroim.2025.578780","url":null,"abstract":"<div><h3>Background:</h3><div>The link between thyroid autoimmunity and Alzheimer’s disease (AD) biomarkers in euthyroid individuals is poorly understood. We investigated the independent and interactive effects of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) on core cerebrospinal fluid (CSF) biomarkers of AD pathology.</div></div><div><h3>Methods:</h3><div>We analyzed CSF biomarkers (A<span><math><mi>β</mi></math></span>1–42, A<span><math><mi>β</mi></math></span>1–40, T-tau, and P-tau181) measured using validated ELISA assays (Fujirebio) in 114 euthyroid, amyloid-positive participants stratified by antibody status. Associations were assessed using multiple linear regression and four-group cross-classification analyses, adjusting for age and gender.</div></div><div><h3>Results:</h3><div>TPOAb positivity was independently associated with a significantly lower CSF A<span><math><mi>β</mi></math></span>1-42/A<span><math><mi>β</mi></math></span>1-40 ratio (mean ± SD: 0.04 ± 0.01 vs. 0.05 ± 0.02; adjusted p=0.022; Cohen’s d = −0.65), indicating more advanced amyloid pathology. Importantly, we identified a novel interaction modulating tau pathology: isolated positivity for either TPOAb or TgAb was linked to elevated P-tau181, but this effect was significantly attenuated in subjects positive for both antibodies (interaction p=0.037).</div></div><div><h3>Conclusion:</h3><div>Thyroid autoimmunity is associated with AD neuropathological changes independent of thyroid hormone status. The specific association of TPOAb with amyloid pathology and the complex interplay between antibodies on tau pathology highlight previously unrecognized mechanisms. These findings, pending validation in longitudinal studies, suggest thyroid antibody screening in elderly euthyroid individuals may aid in identifying those at higher risk for Alzheimer’s pathology, potentially facilitating earlier detection and intervention.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578780"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345895","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":"Neuronal inflammation-associated biomarkers in cerebrospinal fluid of patients with acute and chronic inflammatory demyelinating polyneuropathies","authors":"Ümit Atasever ,&nbsp;Canan Akünal ,&nbsp;Hayriye Soytürk","doi":"10.1016/j.jneuroim.2025.578756","DOIUrl":"10.1016/j.jneuroim.2025.578756","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated polyneuropathies such as acute and chronic inflammatory demyelinating polyneuropathy are challenging to diagnose and treat effectively.</div></div><div><h3>Objective</h3><div>To investigate the diagnostic value of certain biomarkers associated with neuronal inflammation in patients with inflammatory demyelinating polyneuropathy.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The CSF levels of NfL, NfH, GFAP, SM, and BDNF in the AIDP group were significantly higher than those in the PTC group (<em>p</em> &lt; 0.05). In the CIDP group, CSF NfL, GFAP, and SM levels were significantly elevated compared to the PTC group (p &lt; 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 &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578756"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057158","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":"d-serine prevents cognitive impairment in a mouse model of NMDAR encephalitis","authors":"Hanyu Luo,&nbsp;Ziyao Han,&nbsp;Jiaxin Yang,&nbsp;Xiaoyue Yang,&nbsp;Yuhang Li,&nbsp;Dishu Huang,&nbsp;Ran Ding,&nbsp;Li Cheng,&nbsp;Jiannan Ma,&nbsp;Li Jiang","doi":"10.1016/j.jneuroim.2025.578768","DOIUrl":"10.1016/j.jneuroim.2025.578768","url":null,"abstract":"<div><h3>Objective</h3><div>Despite effective immunotherapy, many patients with anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor (NMDAR) encephalitis continue to have persistent cognitive deficits. This study investigated whether <span>d</span>-serine administration can ameliorate cognitive impairment in a mouse model of anti-NMDAR encephalitis.</div></div><div><h3>Methods</h3><div>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 <span>d</span>-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.</div></div><div><h3>Results</h3><div>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 <span>d</span>-serine treatment. Patient-derived anti-NMDAR antibodies reduced synaptic NMDAR clusters and membrane NMDAR1 expression in hippocampus, whereas <span>d</span>-serine administration produced only a modest, non-significant increase in these measures. In contrast, <span>d</span>-serine significantly restored phosphorylation of CaMKII, ERK, and CREB that was suppressed by anti-NMDAR antibodies.</div></div><div><h3>Conclusion</h3><div><span>d</span>-serine effectively ameliorates cognitive impairment induced by anti-NMDAR antibodies, likely by restoring NMDAR-mediated CaMKII/ERK/CREB signaling. These findings support <span>d</span>-serine as a potential adjunct to immunotherapy for patients with anti-NMDAR encephalitis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578768"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227059","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":"Peripheral CD56dimCD16+ NK cells correlate with serum NfL and ALS progression: An exploratory immunophenotyping analysis","authors":"Ryota Tamura ,&nbsp;Ryota Taguchi ,&nbsp;Tomohiro Yamada ,&nbsp;Hideki Wada ,&nbsp;Takashi Ayaki ,&nbsp;Ryosuke Takahashi ,&nbsp;Makoto Urushitani","doi":"10.1016/j.jneuroim.2025.578779","DOIUrl":"10.1016/j.jneuroim.2025.578779","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral immune dysregulation may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), yet, specific immunophenotypes correlated with disease progression remain unclear. We conducted an exploratory analysis to identify peripheral immune cell subsets correlated with ALS progression and serum biomarkers.</div></div><div><h3>Methods</h3><div>Multicolor flow cytometry was used to evaluate 55 immune cell subsets in peripheral blood from 16 ALS patients. We assessed correlation with clinical progression (defined by monthly decline in the ALS Functional Rating Scale-Revised) and serum biomarkers: neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and estimated glomerular filtration rate (eGFR).</div></div><div><h3>Results</h3><div>CD56^dimCD16⁺ natural killer (NK) cells were inversely correlated with both ΔALSFRS-R and serum NfL, and also showed a significant correlation with GFAP. Naive B cells positively correlated with ΔALSFRS-R. Monocyte subsets were differentially correlated with eGFR. Among all cells examined, CD56^dimCD16⁺ NK cells were the only subset significantly correlated with three clinical and biological measures.</div></div><div><h3>Conclusions</h3><div>CD56^dimCD16⁺ NK cells showed consistent correlations with ALS progression markers, although this exploratory study has small sample size and lacks healthy and disease controls, limiting conclusions in terms of statistical power and ALS-specificity about the observed immune alterations. These preliminary findings support the utility of immunophenotyping in ALS biomarker research and warrant validation in larger cohorts.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578779"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313109","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":"Live MOG-IgG cell-based assay: Comparison across flow cytometers and diagnostic validation on high-sensitivity full spectrum flow cytometry","authors":"Elisha Siwan ,&nbsp;Asawin Tungpoomjaruswong ,&nbsp;Vera Merheb ,&nbsp;Fiona X.Z. Lee ,&nbsp;Fakhria Kakar ,&nbsp;Mark Acebes ,&nbsp;Russell C Dale ,&nbsp;David McDonald ,&nbsp;Sudarshini Ramanathan ,&nbsp;Ming-Wei Lin ,&nbsp;David A Brown ,&nbsp;Fabienne Brilot","doi":"10.1016/j.jneuroim.2025.578760","DOIUrl":"10.1016/j.jneuroim.2025.578760","url":null,"abstract":"<div><div>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, <em>p</em> = 0.04) and Aurora (12-fold, <em>p</em> = 0.0001), albeit all MFIs correlated (<em>p</em> &lt; 0.0001; R² = 0.99). Interestingly, the high detection range was attributed to technology, not laboratory environments (<em>p</em> &gt; 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 (<em>p</em> &lt; 0.001; R² ≤ 0.99), regardless of the analysis software (<em>p</em> &lt; 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.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578760"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109170","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}