Abstract
Antibodies and oxidative stress are hallmarks of multiple sclerosis (MS) lesions. We aimed to clarify the relation between them, their role in MS patients and to investigate their specificity, comparing MS with classical neurodegenerative diseases (ND). Brain samples from 14 MS cases, 6 with ND and 9 controls (without neurological diseases). Immunohistochemistry assays were used to detect oxidized lipids (EO6), IgG and IgM, oligodendrocytes (Olig2), axons (NF, neurofilament) and cellular (TUNEL) and axonal damage (APP, amyloid precursor protein). We did not observe EO6 in controls. All samples from MS patients showed EO6 in oligodendrocytes and axons within lesions. We did not detect co-localization between EO6 and antibodies. Neither did we between EO6 and TUNEL or APP. 94.4% of TUNEL-positive cells in normal appearing white matter were also stained for IgG and 75.5% for IgM. IgM, but not IgG, co-localized with APP. EO6 was associated with axonal damage in amyotrophic lateral sclerosis (ALS). We did not observe association between antibodies and cellular or axonal damage in ND patients. MS patients showed a higher number of B cells and plasma cells in the lesions and meninges than controls. The number of B cells and plasma cells was associated with the presence of antibodies and with the activity of the lesions. We observed a main role of B lymphocytes in the development of MS lesions. Antibodies contribute to the oligodendrocyte and axonal damage in MS. Oxidative stress was associated with axonal damage in ALS.
Highlights
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the Central Nervous System (CNS)
Neither did we between EO6 and transferase dUTP nick end labeling (TUNEL) or amyloid precursor protein (APP). 94.4% of TUNEL positive cells in normal appearing white matter were stained for IgG and 75.5% for IgM
Oxidative stress was associated with axonal damage in amyotrophic lateral sclerosis (ALS)
Summary
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the Central Nervous System (CNS). 2004; Gay et al 1997) and normal appearing white matter (Sádaba et al 2012) and were associated with activated complement factors and foamy macrophages (Breij et al 2008; Storch et al 1998; Sádaba et al 2012) The source of these antibodies is unknown but it have been described follicle-like structures in the meninges of MS patients (Magliozzi et al 2007; Prineas 1979; Serafini et al 2004), plasma cells in the lesions (Esiri 1977) and increased activated and memory B cells in the CSF (Haas et al 2011). We aimed to clarify the relation between them, their role in MS patients, and to investigate their specificity, comparing MS with classical neurodegenerative diseases (ND)
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