Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: unknown, P. 578613 - 578613
Published: April 1, 2025
Language: Английский
Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(5), P. 269 - 287
Published: April 12, 2024
Language: Английский
Citations
111
Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(1), P. 1 - 20
Published: April 3, 2024
Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of disease underlies progression disability, which proceeds relentlessly independently clinical radiological relapses (PIRA). The complex system pathological events driving "chronic" worsening likely linked with early accumulation compartmentalized inflammation within central nervous as well insufficient repair phenomena mitochondrial failure. These mechanisms are partially lesion-independent differ those causing formation new focal demyelinating lesions; they lead to neuroaxonal dysfunction death, myelin loss, glia alterations, finally, neuronal network outweighing (CNS) compensatory mechanisms. This review aims provide an overview state art neuropathological, immunological, knowledge about underlying activity, focusing on possible biomarkers their translation into practice. ANN NEUROL 2024;96:1-20.
Language: Английский
Citations
28
Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(740)
Published: March 27, 2024
One of the biggest challenges in managing multiple sclerosis is heterogeneity clinical manifestations and progression trajectories. It still remains to be elucidated whether this reflected by discrete immune signatures blood as a surrogate disease pathophysiology. Accordingly, individualized treatment selection based on immunobiological principles not feasible. Using two independent multicentric longitudinal cohorts patients with early ( n = 309 discovery 232 validation), we were able identify three distinct peripheral immunological endophenotypes combination high-dimensional flow cytometry serum proteomics, followed unsupervised clustering. Longitudinal paraclinical follow-up data collected for revealed that these associated trajectories inflammation versus structural damage. Investigating capacity immunotherapies normalize endophenotype-specific effect sizes illustrated limited interferon-β endophenotype 3–related signatures. who fell into 3 subsequently treated exhibited higher MRI activity over 4-year compared other therapies. We therefore propose ascertaining patient’s signature before immunomodulatory initiation may facilitate prediction enable personalized decisions pathobiological principles.
Language: Английский
Citations
15
Current Opinion in Neurology, Journal Year: 2024, Volume and Issue: 37(3), P. 189 - 201
Published: March 27, 2024
Research in multiple sclerosis (MS) has long been predicated on clinical groupings that do not reflect the underlying biologic heterogeneity apparent within patient populations. This review explicates various levels of explanation through which spectrum disease is described and investigated both above below threshold detection, as framed by topographical model MS, to help advance a cogent mechanistic framework.
Language: Английский
Citations
12
Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(4), P. 101490 - 101490
Published: April 1, 2024
While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning inner plexiform layer (IPL) as early feature inflammatory demyelination—prior to symptom onset. As domains anatomically segregated retina can be monitored longitudinally, hypothesize IPL could represent a biomarker MS. Leveraging our dataset with over 800 participants enrolled more than 12 years, atrophy directly propose is functional decline. blood proteome-wide analysis, demonstrate strong correlation between demyelination, glial activation, synapse independent neuroaxonal injury. In summary, monitoring biologically relevant approach reflects potential driver progression.
Language: Английский
Citations
10
The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 44, P. 101009 - 101009
Published: Aug. 23, 2024
Multiple sclerosis (MS) is an immune-mediated inflammatory and degenerative disorder of the central nervous system (CNS) with heterogeneous clinical manifestations. In last decade, landscape cerebrospinal fluid (CSF) blood biomarkers as potential key tools for MS diagnosis, prognosis treatment monitoring has evolved considerably, alongside magnetic resonance imaging (MRI). CSF analysis not only to provide information on underlying immunopathology disease exclude differential diagnoses, but also predict risk future relapses disability accrual, guide therapeutic decisions thus improve patient outcomes. This Series article overviews biological framework current applicability MS, exploring their role in molecular characterisation disease. We discuss recent advances field neurochemistry that enabled detection brain-derived proteins blood, opening door much more efficient longitudinal monitoring. Furthermore, we identify challenges application a real-world setting, while offering recommendations harnessing full paraclinical management personalise treatment.
Language: Английский
Citations
10
Multiple Sclerosis and Related Disorders, Journal Year: 2024, Volume and Issue: 87, P. 105644 - 105644
Published: April 26, 2024
BackgroundThis study aimed to evaluate the utility of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1) and total tau (tTAU) serum concentrations as approximation for cerebrospinal fluid (CSF) respective biomarkers in context neuroinflammation multiple sclerosis (MS).MethodsNfL, GFAP, UCHL1 tTAU CSF were measured 183 patients (122 with neuroinflammatory disease 61 neurological or somatoform controls) using single molecule array HD-1 analyzer (Quanterix, Boston, MA). Spearman's rank correlations computed between concentrations. In a second step, effects age, BMI, gadolinium-enhancing lesions MRI, integrity blood–brain barrier (BBB) presence acute relapse accounted by computing partial correlations. The analyses repeated subsample consisting MS phenotype only (n=118). EDSS, activity considered additional covariates. Receiver operating characteristic (ROC) analysis was performed each serum/CSF biomarker concentration assess how well particular differentiates from controls. Correlations levels area under curve (AUC) values compared different z-test statistics.ResultsSerum correlated positively NfL (r=0.705, p<0.01) GFAP (r=0.259, p<0.01). Correlation coefficients significantly higher than (z=5.492, We found no significant serum-CSF tTAU. After adjusting covariates, results remained unchanged. focusing on patients, replicated. ROC demonstrated similarly acceptable performance differentiating AUC other biomarkers.ConclusionNfL but not are associated biomarker. exhibits more robust its independently BBB integrity, clinical radiological Both differentiate
Language: Английский
Citations
8
Clinical & Experimental Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 8, 2025
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS, whereby clinical activity primarily monitored by magnetic resonance imaging (MRI). Given limitations associated with implementing and acquiring novel emerging biomarkers in routine practice, discovery biofluid may offer more simple cost-effective measure that would improve accessibility, standardization, patient care. Extracellular vesicles (EVs) are nanoparticles secreted from cells under both homeostatic pathological states, have been recently investigated as MS. The objectives this study were to longitudinally levels specific immune cell-derived EVs MS provide evidence EV sub-populations serve activity, axonal injury, and/or disability. Our results demonstrate rate disability negatively correlates changes circulating CD3+ within plasma. Additionally, numbers CD4+ decrease individuals increasing pNfL overtime magnitude increase plasma CD8+ EVs. Finally, when applying NEDA-3 criteria define active versus stable disease, had significantly elevated compared disease. In summary, analysis subsets method monitor accumulation, injury MS, while also providing insights into pathophysiology cellular/molecular mechanisms influence progression.
Language: Английский
Citations
1
Multiple Sclerosis Journal, Journal Year: 2024, Volume and Issue: 30(6), P. 643 - 645
Published: April 11, 2024
Language: Английский
Citations
6
Annals of Neurology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 16, 2024
Objective To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B‐cell depleting therapy (BCDT) their capacity to prognosticate future progression independent relapse activity (PIRA) events. Methods A total 362 pwMS (1,480 samples) starting BCDT Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP 2,861 control persons (4,943 provided normative data calculate adjusted Z scores. Results Elevated (Z score >1) at 1 year associated a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17–2.78]; p = 0.0079) than elevated sNfL (HR, 1.45 [0.95–2.24], 0.0886) combined model. Independent events, longitudinally increased by 0.49 units per 10 years follow‐up (estimate, [0.29, 0.69], < 0.0001). In patients experiencing PIRA, scores 0.52 versus stable (0.52 [0.22, 0.83], 0.0009). Different trajectories found without (interaction 0.0028), an average decrease 0.92 observed (−0.92 [−1.23, −0.60], 0.0001), whereas remained high. Interpretation lack drop after start are risk PIRA. These findings provide rationale monitoring predict use as outcome clinical trials aiming impact on MS progressive disease biology. ANN NEUROL 2024
Language: Английский
Citations
6