Figure - available from: Frontiers in Neurology
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Screening for serum autoantibodies against oligodendrocytes in patients with MS. IgGs (green) from three PPMS patients (Cases 1–3) and one SPMS patient (Case 4) bound to Nogo A-positive oligodendrocytes (red) in mouse cerebellum, whereas control IgGs from one representative RRMS patient, one representative NMOSD patient, one representative OIND patient with neuro-Behçet's disease, and one representative HC showed no significant immunoreactivity toward Nogo A-positive oligodendrocytes. Nuclei were counterstained with 4′,6-diamidino-2-phenylindole (DAPI) (blue). Scale bars: 50 μm. ANA, antinuclear antibody; CNS, central nervous system; HC, healthy control; IgG, immunoglobulin G; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders; OIND, other inflammatory neurological disorder; PPMS, primary progressive multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.
Source publication
Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical courses and disease severities, it is important to identify biomarkers that predict disease activity and severity. In this study, we asse...
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Citations
... The demyelinating potential of GalC-specific autoantibodies had previously been demonstrated 62,63 , and these antibodies were found to be more common in patients with MS -particularly relapsing-remitting MS -than in healthy controls 64 . These findings are consistent with other studies that detected antibodies to conformational epitopes of oligodendrocytes, myelin and astrocytes in patients with MS [65][66][67][68][69] , and they suggest that pathogenic autoantibodies do exist in MS but further work is necessary to identify their targets. ...
The role of autoantibodies in multiple sclerosis (MS) has been enigmatic since the first description, many decades ago, of intrathecal immunoglobulin production in people with this condition. Some studies have indicated that MS pathology is heterogeneous, with an antibody-associated subtype — characterized by B cells (in varying quantities), antibodies and complement — existing alongside other subtypes with different pathologies. However, subsequent evidence suggested that some cases originally diagnosed as MS with autoantibody-mediated demyelination were more likely to be neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease. These findings raise the important question of whether an autoantibody-mediated MS subtype exists and whether pathogenic MS-associated autoantibodies remain to be identified. Potential roles of autoantibodies in MS could range from specific antibodies defining the disease to a non-disease-specific amplification of cellular immune responses and other pathophysiological processes. In this Perspective, we review studies that have attempted to identify MS-associated autoantibodies and provide our opinions on their possible roles in the pathophysiology of MS. Numerous studies have attempted to identify pathogenic autoantibodies in people with multiple sclerosis (MS), but their results are conflicting. In this Perspective, the authors explore the available evidence and provide their own opinions on a possible role for autoantibodies in MS.
Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.
Background
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks.
Methods
We applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue ( n = 46), sorted neuronal ( n = 54), and glial nuclei ( n = 66) from post-mortem brain tissue of progressive MS patients and controls.
Results
We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls ( P = 0.0024) using the Cortical clock, which held after adjustment for covariates ( P adj = 0.0263). The 4.8-year age acceleration found in MS neurons ( P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls.
Conclusion
While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
