ReviewAnnals of clinical and translational neurology2021
Mechanistic underpinning of an inside-out concept for autoimmunity in multiple sclerosis.
Review in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Cytokine Profile in Patients with Multiple Sclerosis Following Exercise: A Systematic Review of Randomized Clinical Trials.International journal of environmental research and public health · 2022Pooled it
- Exploring causal correlations between oily fish intake and multiple sclerosis: A two-sample Mendelian randomization study.Asia Pacific journal of clinical nutrition · 2026Article
- Apigenin as a Potential Modulator of Neuroinflammation in Multiple Sclerosis: A Review.Biology · 2026Review
- Understanding the Role of Hypothalamic-Pituitary-Gonadal Axis in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.Biomedicines · 2026Review
- Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.Neural regeneration research · 2026Article
- Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.Journal of neuropathology and experimental neurology · 2026Article
- Label-free tracking of subcortical white matter degradationBiomedical optics express · 2026Article
- Multiple sclerosis and autoimmunity: a reappraisal of the evidence.Frontiers in immunology · 2026Review
- Multiple sclerosis: molecular pathogenesis and therapeutic intervention.Signal transduction and targeted therapy · 2025Review
- Mitochondria-targeted antioxidant skq1 reverses functional impairment and histopathological insults in a chronic animal model of multiple sclerosis.Metabolic brain disease · 2025Article
- The Relationship Between Autoimmune Disorders and Multiple Sclerosis: Clinical Insights and Therapeutic Approaches.Brain sciences · 2025Article
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- Central TYK2 inhibition identifies TYK2 as a key neuroimmune modulator.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Enhancing remyelination in multiple sclerosis via M1 muscarinic acetylcholine receptor.Molecular pharmacology · 2025Review
- Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025Review
- (Poly)phenols and Multiple Sclerosis: Results from an Observational Cross-Sectional Study.Antioxidants (Basel, Switzerland) · 2025Article
- Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Identification of shared pathogenic signatures of multiple sclerosis and chronic obstructive pulmonary disease: an integrated transcriptomic analysis of blood specimens.Molecular genetics and genomics : MGG · 2024Article
- Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis.Cell stem cell · 2024Article
- EBV infection drives MS pathology: No.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuroinflammatory disease multiple sclerosis is driven by autoimmune pathology in the central nervous system. However, the trigger of the autoimmune pathogenic process is unknown. MS models in immunologically naïve, specific-pathogen-free bred rodents support an exogenous trigger, such as an infection. The validity of this outside-in pathogenic concept for MS has been frequently challenged by the difficulty to translate pathogenic concepts developed in these models into effective therapies for the MS patient. Studies in well-validated non-human primate multiple sclerosis models where, just like in humans, the autoimmune pathogenic process develops from an experienced immune system trained by prior infections, rather support an endogenous trigger. Data reviewed here corroborate the validity of this inside-out pathogenic concept for multiple sclerosis. They also provide a plausible sequence of events reminiscent of Wilkin's primary lesion theory: (i) that autoimmunity is a physiological response of the immune system against excess antigen turnover in diseased tissue (the primary lesion) and (ii) that individuals developing autoimmune disease are (genetically predisposed) high responders against critical antigens. Data obtained in multiple sclerosis brains reveal the presence in normally appearing white matter of myelinated axons where myelin sheaths have locally dissociated from their enwrapped axon (i.e., blistering). The ensuing disintegration of axon-myelin units potentially causes the excess systemic release of post-translationally modified myelin. Data obtained in a unique primate multiple sclerosis model revealed a core pathogenic role of T cells present in the normal repertoire, which hyper-react to post-translationally modified (citrullinated) myelin-oligodendrocyte glycoprotein and evoke clinical and pathological aspects of multiple sclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.