OBJECTIVE:To determine the pooled prevalence of cognitive impairment (CI) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) relative to relapsing-remitting multiple sclerosis (RRMS) and identify the primary cognitive domains impaired. METHODS:Electronic databases were searched from inception to January 2026 for studies featuring adults with MOGAD evaluated with formal neuropsychological testing. Impairment was organized into six cognitive domains. Prevalence was estimated using logit transformation and compared with RRMS via a two-proportion Z-test. Risk of bias was assessed and certainty of evidence was summarized using GRADE. RESULTS:Among 958 unique records, 6 met inclusion criteria. The pooled prevalence of MOGAD CI was 22% (95% CI 13-35%), with 51% (95% CI 35% - 67%) demonstrating impairment in at least 1 cognitive domain. Verbal memory (19% [CI 10%-34%]) and working memory/processing speed (19% [CI 10%-31%]) were most frequently affected. The prevalence of CI was 10.5% lower than RRMS (32.5% [CI 29-36%], p = 0.11). CONCLUSION:Approximately 22% of adults with MOGAD experience CI, with verbal memory and processing speed among the key cognitive domains involved. Future large-scale prospective studies should determine the prevalence of MOGAD-related CI across the age span and clinical spectrum and compared with other acquired demyelinating syndromes.
Microglia are the resident immune cells of the brain and serve as key regulators of innate immune responses within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that plays a central role in innate immunity, and its excessive activation contributes to the pathogenesis of neurodegenerative diseases. Nilotinib, a second-generation tyrosine kinase inhibitor, has recently attracted attention due to its neuroprotective and immunomodulatory properties in the CNS. In the present study, we investigated the effects of nilotinib on NLRP3 inflammasome activation, GSDMD/NINJ1-mediated pyroptosis, NF-κB signaling, BAG3-dependent aggrephagy, and ESCRT-III-mediated plasma membrane repair in LPS plus ATP-induced murine N9 microglial cells. Our findings demonstrated that nilotinib significantly attenuated NLRP3 inflammasome activation, as evidenced by reduced NLRP3 expression, decreased caspase-1 activation, and suppressed secretion of proinflammatory cytokines IL-1β and IL-18 through modulation of the IκBα/NF-κB signaling axis. Furthermore, nilotinib markedly inhibited pyroptotic cell death by reducing GSDMD-N and NINJ1 expression, thereby preserving membrane integrity. In parallel, nilotinib enhanced BAG3-dependent selective autophagy and increased LC3B expression, suggesting activation of aggrephagy pathways involved in the clearance of inflammasome-associated components. Notably, nilotinib also restored VPS4A expression, indicating activation of ESCRT-III-mediated plasma membrane repair mechanisms. Collectively, our results reveal that nilotinib exerts a multi-layered regulatory effect on microglial inflammatory responses by suppressing inflammasome activation and pyroptosis while promoting autophagy-dependent clearance and membrane repair pathways. These findings highlight a novel integrative mechanism linking autophagy, pyroptosis, and membrane repair in the neuroprotective actions of nilotinib.
Glioblastoma (GB), defined here primarily as adult-type Isocitrate dehydrogenase-wildtype high-grade glioma, according to the 2021 World Health Organization classification, is an aggressive primary brain tumor characterized by local and systemic immunosuppression, therapeutic resistance, and poor clinical outcomes. Although considerable attention has focused on adaptive immune responses in GB, innate immune cells centrally regulate the tumor microenvironment. They may influence tumor progression, immune evasion, and treatment response. The strength of evidence varies substantially across innate immune populations, ranging from well-characterized myeloid compartments, such as tumor-associated macrophages, dendritic cells, myeloid-derived suppressor cells, and neutrophils, to less explored granulocytic and lymphoid subsets, including natural killer cells, innate lymphoid cells, eosinophils, mast cells, and basophils. In this review, we discuss the context-dependent roles of these cells in tumor surveillance and promotion, their interactions with GB stem-like cells, their contributions to immunosuppression and therapeutic resistance, and their potential relevance as prognostic biomarkers or therapeutic targets. By integrating clinical observations with experimental evidence, we highlight current strategies to reprogram innate immunity in GB and identify key limitations that must be addressed before innate immune-based approaches can be translated more effectively into clinical practice.
Sporadic Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disorder characterized by numerous pathological processes occurring both in the brain and in the periphery, including chronic local or systemic inflammation, cerebrovascular impairment, oxidative stress, mitochondrial dysfunction, amyloidosis, synaptic and neuronal network dysfunction, metabolic syndrome, and disrupted cell signaling pathways. Although these mechanisms have been extensively studied, the contribution of the peripheral immune system to the etiology and progression of AD remains poorly understood. Emerging evidence suggests that pathological events in the brain, such as amyloid and phosphorylated tau accumulation, neurodegeneration, and neuroinflammation, may trigger systemic immune responses that alter the distribution and function of peripheral immune cells. However, available findings remain inconsistent. In the present study, we examined age-dependent alterations in peripheral blood immune cell populations in Tg-SwDI mice, a transgenic model of AD. We documented for the first time that transgenic mice exhibited increased proportions of neutrophils and an elevated neutrophil-to-lymphocyte ratio (NLR), along with reduced percentages of T lymphocytes compared with wild-type controls. Furthermore, significant differences in T-cell subpopulations were observed between Tg-SwDI and wild-type animals. Our findings are partially consistent with reported clinical observations in patients with AD. Because no single transgenic mouse model fully recapitulates the complex pathology of AD, and many therapeutic approaches successful in preclinical models have failed in clinical trials, a detailed characterization of disease-related alterations in each model is essential for selecting the most appropriate model to investigate specific mechanisms or therapeutic approaches.
Myasthenia gravis (MG) is an autoimmune disorder characterized by antibody-mediated neuromuscular dysfunction, but the systemic immune landscape and underlying mechanisms remain unclear. Here we analyzed single-cell RNA-seq data from peripheral blood mononuclear cells of MG patients and healthy controls to characterize immune cell composition, transcriptional programmes and intercellular communication. Among 206,472 high-quality cells, we observed significant immune dysregulation in MG, including expansion of innate populations, reduction of naïve T cells, and increases in memory T cells and immature B cells. Pathway analysis highlighted heightened inflammatory signalling, and cell-cell communication analysis revealed stronger interactions, especially among T and B cell subsets. Subclustering identified substantial T-cell dysregulation, characterized by enhanced effector-associated transcriptional programs in CD8+ T cells. Integrative machine learning and weighted gene co-expression network analysis pinpointed PLEK as a key hub gene upregulated in CD8+ effector T cells and associated with T-cell receptor signalling. Clinical validation confirmed elevated PLEK expression, which positively correlated with disease severity. Collectively, this study provides a systems-level view of immune dysregulation in MG, highlighting enhanced intercellular communication, T-cell dysregulation, and PLEK as a potential molecular marker associated with CD8+ T-cell activation and disease severity, offering insights into MG pathogenesis and therapeutic targets.
INTRODUCTION:Previous studies have reported conflicting results regarding visual evoked potential (VEP) and OCT abnormalities in patients with Behçet's disease (BD). This study aimed to address these discrepancies by investigating subclinical optic neuropathy and retinal dysfunction in Behçet's disease using VEP and OCT. METHODS:Seventy-five patients with BD and 40 age- and sex-matched healthy controls underwent comprehensive neurological and ophthalmological examinations. VEP was used to assess P100 latency and amplitude, while peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses were measured using OCT. Subgroup analyses were performed according to neurological and ocular involvement. RESULTS:Mean disease duration was 9 ± 6 years (0-26 years). No significant differences were observed in P100 latency or amplitude between patients with BD and healthy controls, nor between BD subgroups. Subclinical optic neuropathy, defined as prolonged P100 latency exceeding mean + 2 SD, was identified in only one patient (1.33%) in just BD group. Mean RNFL and GCC thicknesses were comparable between groups and subgroups. CONCLUSIONS:Despite its inflammatory nature, silent optic neuropathy detectable by VEP appears to be uncommon in BD. Retinal involvement may not be expected in Behçet's disease patients with mild ocular involvement, no active ocular involvement, and an average disease duration of less than 10 years. Long term follow-up studies involving larger number of patients, especially with neurologic involvement, are needed.
BACKGROUND:Early neurological dysfunction defines early brain injury after subarachnoid hemorrhage (SAH). Neutrophil extracellular trap (NET) formation increasingly appears to operate as a neuroimmune amplifier rather than a passive marker. We tested whether dual-pathway attenuation of NETosis is associated with suppression of immunothrombotic, redox, and blood-CSF barrier injury and with improved early neurological function after experimental SAH. METHODS:Male Sprague-Dawley rats underwent endovascular perforation SAH and were allocated to Sham+Vehicle, SAH + Vehicle, SAH + DNase-L (2.5 mg/kg q12h, i.p.), SAH + DNase-H (5 mg/kg q12h, i.p.), SAH + Colchicine (0.5 mg/kg q24h, i.p.), or SAH + DNase-H + Colchicine. Treatments started 1 h after SAH. Behavior at 24 h (mNSS, open-field) was assessed in a pre-specified, blinded subcohort (n = 6/group). Multidomain biomarker quantification used a parallel blinded subcohort (n = 6/group). One-way ANOVA with Tukey's HSD was used; biomarker panels were Benjamini-Hochberg FDR-corrected. RESULTS:SAH was associated with rapid increases in plasma NET-associated markers, with cfDNA peaking at 3 h (520 ± 60 vs 135 ± 12 ng/mL in Sham; p < 0.001). Immunothrombotic, redox and blood-CSF barrier indices were markedly elevated at 24 h. The combination group showed the most favorable profile: mNSS 4.17 ± 0.75 vs 11.50 ± 1.05 (Hedges' g = 7.42, 95% CI 5.90-8.94; p < 0.001). Composite z-score correlated with mNSS (Spearman ρ = 0.92, p < 0.001). CONCLUSIONS:Dual-pathway modulation of NETosis is associated with attenuated multidomain neuroimmune readouts and improved early neurological function after experimental SAH, consistent with NETosis as a candidate mechanistic node in early brain injury.
INTRODUCTION:Vitamin D deficiency (VDD) and neuroinflammation are emerging as key contributors in the pathophysiology of Parkinson's disease (PD). Characterized by both motor and non-motor symptoms, PD is marked by dopaminergic neuronal loss and α-synuclein accumulation. VD exerts neuroprotective effects by preserving dopaminergic neurons, enhancing neurotransmission, and reducing neuroinflammation. Its biological activity is primarily mediated through the Vitamin D Receptor (VDR), which functions as a transcription factor upon activation. This study investigates ethnic variability of two important VDR polymorphisms and their association with PD. METHODS:Literature revealed ethnic variations in the association between VDR polymorphisms and PD. 100 PD patients (Montreal Cognitive Assessment [MoCA ≤23]; H&Y ≤ 4) and 100 matched controls were genotyped for VDR-FokI (rs2228570) and VDR-BsmI (rs1544410) using PCR-RFLP, confirmed through sequencing. VD levels were quantified for 35 PD and 25 controls. RESULTS:Significant allelic differences were found in both FokI (C vs. T, p = 0.001) and BsmI (A vs. G, p = 0.002). Genotypic variation was significant in FokI (p = 0.003) and BsmI (p = 0.004). FokI genotypes correlated significantly with cognitive scores (MoCA, p = 0.03), with CT and TT genotypes associated with poorer outcomes. Further analysis showed males and patients with lower BMI, more vulnerable. FokI influence cognitive assessment in females. Hypovitaminosis D was prevalent in PD patients than controls. CONCLUSIONS:VDR-FokI (rs2228570) exhibits a significant association with cognitive vulnerability in PD cohort, emerging as a potential genetic risk marker, suggesting link between this variant and cognitive status. However, larger longitudinal cohorts are imperative to validate the prognostic utility of VDR and VD pathways. SIGNIFICANCE STATEMENT:Parkinson's disease (PD) is increasingly recognized as a multifactorial neurodegenerative disorder in which genetic susceptibility and modifiable environmental factors interact to influence disease progression. However, the contribution of vitamin D receptor (VDR) genetic variability to PD risk and cognitive dysfunction remains poorly understood, particularly in the Indian population. In this study, we demonstrate that two VDR polymorphisms, FokI (rs2228570) and BsmI (rs1544410), are significantly associated with PD, while vitamin D deficiency is more prevalent among affected individuals. Importantly, the FokI variant showed a strong association with cognitive impairment, with CT/TT carriers exhibiting significantly lower MoCA scores, identifying this polymorphism as a potential marker of cognitive vulnerability in PD. These findings advance our understanding of how vitamin D signalling influences neurodegeneration and cognitive decline, highlighting a biologically plausible gene-environment interaction in PD. Beyond movement disorders, this work underscores the broader relevance of vitamin D-dependent mechanisms in brain health and supports the development of genotype-informed precision medicine strategies for neurodegenerative diseases.
BACKGROUND:Chronic pain is a frequent complication of longitudinally extensive transverse myelitis (LETM). In neuromyelitis optica spectrum disorder-associated transverse myelitis (NMOSD-TM), pain has been largely attributed to AQP4-IgG-mediated inflammation. However, pain burden in double-seronegative LETM (DSN-LETM) remains poorly characterized. METHODS:In this prospective study, patients with LETM (≥3 vertebral segments) in remission were enrolled and classified as DSN-LETM (negative for anti-aquaporin-4 and anti-MOG antibodies) or seropositive NMOSD-TM. Pain was assessed using PainDETECT and the Brief Pain Inventory. Health-related quality of life (HRQoL) was evaluated using EuroQoL-5D at baseline and 6-12 months. RESULTS:Fifty-four patients were included (DSN-LETM, n = 9; NMOSD-TM, n = 45; median age 57 years). Compared with NMOSD-TM, DSN-LETM had shorter cumulative spinal cord lesion length and less cervical involvement, indicating lower structural lesion burden. Despite this, all DSN-LETM patients reported chronic pain (100%), compared with 87% in NMOSD-TM. Numbness was more prominent in DSN-LETM. In NMOSD-TM, pain severity was significantly associated with clinical disability and lesion burden, whereas no such associations were observed in DSN-LETM. Greater pain severity was associated with poorer HRQoL in both groups and remained stable over a median 7-month follow-up. CONCLUSION:Chronic pain in DSN-LETM is substantial and persistent despite limited lesion burden, highlighting a dissociation between structural inflammatory burden and pain severity. These findings suggest that pain in DSN-LETM may not be adequately captured by conventional measures of lesion burden, underscoring the importance of proactive pain assessment and management.
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a potentially severe autoimmune encephalitis that may rapidly progress to critical illness. We report a young patient with severe anti-NMDAR encephalitis complicated by seizures, psychiatric symptoms, behavioral disturbance, dyskinesia, and dysautonomia. Despite first-line immunotherapy with intravenous methylprednisolone and intravenous immunoglobulin, the patient remained severely disabled. Peripheral blood analysis showed elevated C5a and soluble C5b-9 levels, suggesting activation of the terminal complement pathway. After treatment with eculizumab, a monoclonal antibody targeting complement component C5, seizure ceased and psychiatric symptoms improved rapidly. These findings suggest that complement inhibition may facilitate rapid neurological recovery and may represent a potential therapeutic strategy for selected patients with severe anti-NMDAR encephalitis.
Background The mechanisms underlying peripheral neuropathic pain (NP) are complex, and current knowledge heavily relies on animal models of acute traumatic nerve injuries, which differ substantially from common, progressive neuropathies such as entrapment neuropathies (EN). Identifying human-translatable biomarkers of NP and validating them across different neuropathy models is therefore of particular interest. MicroRNAs (miRNAs) have emerged as promising biomarkers in several pathologies. Specifically, miR-30c-5p has shown alterations in animal models of NP and in patients with vascular neuropathy; however, it has not yet been evaluated in individuals with EN. Methods This cross-sectional study aims to determine whether blood-based miR-30c-5p levels differ between patients with carpal tunnel syndrome (CTS) and age- and sex-matched healthy controls. A total of 60 participants (40 CTS patients, 20 controls) will be recruited at Hospital 12 de Octubre (Madrid, Spain). All participants will undergo a comprehensive somatosensory assessment, including sensory testing and conditioned pain modulation. CTS patients additionally completed neuropathic pain questionnaires (DN4 and NPSI) and nerve conduction studies according to clinical protocols. Finally, a 10 mL venous blood sample will be collected from each participant for the quantification of plasma miR-30c-5p concentration using qPCR. Ethical approval was obtained from the Hospital 12 de Octubre Ethics Committee on March 19th, 2024 (reference 24/051). Discussion This study will clarify whether miR-30c-5p is altered in patients with CTS, potentially contributing to NP pathophysiology in EN. Positive findings would support further research aimed at validating miR-30c-5p as a biomarker for NP, regardless of its underlying etiology.
Treatment-resistant depression (TRD) represents a major clinical challenge characterised by inadequate response to conventional antidepressant therapies and high relapse rates. Emerging evidence suggests that TRD may extend beyond monoaminergic dysfunction and may involve dysregulation of the HPA axis, neuroinflammation, impaired neuroplasticity, and disruption of the gut-brain axis (GBA). Gut dysbiosis has been associated with treatment resistance through alterations in monoamine turnover, immune signalling, intestinal barrier integrity, and drug-microbiome interactions affecting antidepressant bioavailability. This review integrates emerging evidence supporting targeted modulation of the GBA as a mechanistically informed strategy for TRD. Specific microbial strains (e.g., Christensenella minuta, Akkermansia muciniphila, Bifidobacterium breve CCFM1025), microbial metabolites (e.g., indole-3-propionic acid, indole-3-lactic acid, anserine), and phytochemicals (e.g., curcumin, matrine, salidroside) are discussed for their proposed roles in modulating neuroendocrine signalling, neuroinflammation, and synaptic plasticity. The review also highlights emerging peripheral biomarkers, including the kynurenine/tryptophan ratio, serum metabolomics, and lymphocyte serotonin transporter clustering, as candidate tools for stratified psychiatry. Most of the evidence discussed in this review comes from animal studies, in vitro systems, and computational analyses, while direct evidence in patients with treatment-resistant depression remains limited. These findings provide important mechanistic insights into gut-brain axis dysfunction but require further validation in human TRD populations. Biomarker-guided and endotype-based approaches targeting the gut-brain axis may offer a useful framework for future research, although their clinical utility has yet to be established.
Glioblastoma (GBM) is characterized by profound immunosuppression and limited responsiveness to conventional T cell-based therapies and immune checkpoint blockade. Here, we establish a human microglial cell line to explore the concept of a brain-adapted platform for chimeric antigen receptor (CAR) expression targeting GBM. We engineered human microglial cells with anti‑carbonic anhydrase IX (CAIX) CARs incorporating either CD28 or 4-1BB costimulatory domains, alone or co-expressing anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Our results demonstrate that CAIX-targeted CAR-engineered microglia-like cells (CAR-MG) mediate potent, antigen-dependent tumor killing in vitro, with CD28-based constructs exhibiting superior antitumor efficacy and a robust pro-inflammatory cytokine profile. Furthermore, local secretion of anti-PD-L1 synergized with CAIX-targeting to significantly reduce tumor burden in vivo - an effect closely associated with the successful reprogramming of infiltrating myeloid cells toward an M1-like anti-tumoral state, evidenced by an increase in the frequency of cells expressing CD38, CD86, and HLA-DR. Notably, the anti-PD-L1 secretory platform downregulated tumor-derived PD-L1, effectively remodeling the immunosuppressive glioblastoma microenvironment. These findings suggest that this engineered microglial cell line platform has the potential to heat the immunologically "cold" GBM microenvironment. Together, these results identify CAIX-targeted engineered CAR-MG as an effective immunotherapeutic approach and support further development of CNS-targeted immune cells to overcome key barriers to cellular immunotherapy in GBM.
Objective In patients with progressive multiple sclerosis (PMS), previous studies reported increased cerebrospinal fluid (CSF) concentrations of inflammatory biomarkers, but these correlated only weakly with structural damage. We aimed to identify inflammatory CSF biomarkers that associate with tissue damage in PMS. Methods We performed four substudies: [1] A cross-sectional exploratory study of patients with primary (PPMS) or secondary progressive MS (SPMS) (n = 38) in whom we explored correlations between CSF concentrations of 1128 proteins and CSF neurofilament light chain (NFL) and myelin basic protein. [2] A cross-sectional confirmatory study where a protein of main interest, chitinase-1 (CHIT1), was analyzed in 104 patients with PPMS (n = 78) or SPMS (n = 26) and compared with 38 symptomatic controls. [3] Associations between CSF concentrations of CHIT1 and other disease biomarkers including CSF- and magnetic resonance imaging (MRI)-based measures of white matter injury in patients with PPMS (n = 59). [4] A longitudinal study of effects of treatment with methylprednisolone, natalizumab, dimethyl fumarate, or placebo on CHIT1 in CSF in patients with PMS. Results Substudy [1] identified three proteins that correlated with CSF NFL: soluble B-cell maturation antigen, CC chemokine ligand 22, and CHIT1. CHIT1 showed a strong correlation with CSF NFL (ρ = 0.61, q = 0.008) and was selected for further analyses. Substudy [2] showed that patients with progressive MS had higher CSF concentrations of CHIT1 than symptomatic controls (all p < 0.001). In substudy [3], CSF concentrations of CHIT1 correlated with increased lesion volume (p < 0.001) and decreased magnetization transfer ratio (p = 0.001) of lesions, decreased fractional anisotropy (p < 0.001) and increased mean diffusivity of normal-appearing white matter (p = 0.044) and lesions (p = 0.005) in patients with PPMS. Substudy [4] showed that natalizumab treatment reduced CSF CHIT1 concentrations (p = 0.005) in PMS. Conclusion CSF CHIT1 concentrations are associated with neuroaxonal and white matter injury in patients with PPMS and responsive to disease-modifying therapy in PMS.
Background Myasthenia Gravis (MG) is an autoimmune disease that damages the neuromuscular junction (NMJ), reduces the transmission of nerve impulses to muscles, and thus causes fluctuating muscle weakness and fatigue. The main types of MG are autoantibodies that target necessary components of the postsynaptic membrane, such as acetylcholine receptors (AChRs) and muscle-specific kinase (MuSK). The above immune-mediated alterations disrupt synaptic transmission and reduce muscle contraction.Study the molecular and cellular mechanisms of MG to find genes that regulate the immune system, cause inflammation, or affect NMJ homeostasis and may serve as biomarkers. These biomarkers can provide more information on the course of a disease and help to customise diagnosis and treatment according to this information. Methods The transcriptomic data in this study were obtained from the Gene Expression Omnibus (GEO) database under accession number GSE85452 (GPL10558), which contains peripheral blood gene expression profiles of MG patients and healthy controls. Differential Expression Analysis was conducted to find genes in *M. fitumendi* related to MG. Preprocess and normalise the raw data before the following comparisons.Mendelian Randomisation (MR) was employed to investigate whether the candidate genes causally affected MG risk. PTGS2 was found to be a protective factor (OR < 1) and selected for further study. Gene set enrichment analysis (GSEA) was then carried out to identify related pathways, and single-sample gene set enrichment analysis (ssGSEA) was used to explore associations with the immune system. Single-cell RNA sequencing (scRNA-seq) was performed to find out which cells expressed PTGS2, how the proportions of different cell types in the MG microenvironment were changed, and what inter-cellular communication occurred.A network-based virtual PTGS2 overexpression analysis was also carried out in MG cells with scTenifoldNet. Single-cell gene regulatory networks were built from the raw count data and denoised by tensor decomposition. PTGS2 regulatory activity increased due to a doubling of the weight of the positive regulatory edge. Genes with an adjusted P-value <0.05 were regarded as significantly altered and subjected to KEGG and Gene Ontology enrichment analysis. Results Using a sensitive threshold of |log₂FC| > 0.38 for the initial screening of the MG transcriptome, a particular set of differentially expressed genes in patients was identified compared with healthy individuals. Mendelian Randomisation analysis also showed that PTGS2 is associated with a reduced risk of MG and has a negative causal association with the disease. Functional enrichment analysis linked PTGS2-associated molecular signatures to immune and inflammatory pathways.Immune infiltration analysis showed variations in the proportion of immune cells in MG, and PTGS2 expression was significantly correlated with several subsets of immune cells. Gene-disease association mapping links PTGS2 to multiple immune-related disorders. Single-cell RNA sequencing also showed cell-type-specific expression and different distributions of PTGS2 in MG patients and healthy controls.Overexpression of virtual PTGS2 mainly modified genes and pathways in the myeloid cell, such as IL-17 signalling, chemotaxis and neutrophil migration. Therefore, PTGS2 may be involved in the regulation of inflammatory myeloid responses in MG. Summary Transcriptome and gene analysis identified PTGS2 as a protective gene for myasthenia gravis. PTGS2 is linked to immune-inflammatory signals, and single-cell data have identified specific cell types in the MG immune microenvironment that express it. Network-based virtual PTGS2 overexpression mainly altered myeloid-associated genes and pathways of IL-17 signalling, chemotaxis and neutrophil migration. PTGS2 may be a biomarker and a possible therapeutic target for MG.
Background The 2024 revision of the McDonald criteria allows the diagnosis of multiple sclerosis (MS) based on dissemination in space alone when ≥4 typical lesion locations are present, raising the question of how lesion burden influences the incremental diagnostic value of cerebrospinal fluid (CSF) analysis. Objective To evaluate the incremental diagnostic value of intrathecal IgG oligoclonal bands (IgGOB) according to lesion burden at MS diagnosis. Methods In this retrospective, cross-sectional, single-centre study, 341 patients undergoing diagnostic evaluation for suspected MS were included. Logistic regression models assessed the associations among lesion burden, intrathecal IgG synthesis and MS diagnosis. Results Lesion burden was strongly associated with MS diagnosis (β = 1.55, p < 0.0001). CSF-restricted IgGOB positivity was associated with lesion burden, but not with disease duration. In a multivariable logistic regression model, both lesion burden (p < 0.0001) and CSF-restricted IgGOB (p < 0.0001) remained independently associated with MS diagnosis (AUC = 0.988). The incremental diagnostic contribution of intrathecal IgG synthesis progressively decreased as lesion burden increased. Conclusions The incremental diagnostic value of intrathecal IgG synthesis is strongly influenced by lesion burden. These findings support a context-dependent interpretation of CSF analysis within the 2024 McDonald diagnostic criteria.
