Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis

Abstract

Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.

Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis

“…Our results also show that increased levels of anti-NF antibodies correlate with low scores on the ALSRS-r scale, which points towards an association of these antibodies with disease severity. This observation is in line with a previous study that shows a significant relationship between ALSFRS-r and serum levels of anti-NF antibodies in ALS patients 11. Furthermore, the association between NF antibody levels and likelihood of death observed in this study could indicate an important role of these antibodies in the pathology of ALS.…”

“…The potential value of immunomonitoring ALS by studying anti-NF-L immunoreactivity draws on the intrinsic stability of antibodies and on their homogeneous distribution in blood and CSF 10. In a small cohort of ALS patients, serum antibodies against NF-L have already been shown to be up-regulated compared to healthy controls 11. Previous studies have shown that serum and CSF anti-NF-L antibodies are elevated in other neurological disorders such as multiple sclerosis 12 13…”

Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes

“…By considering that the SH2 domain in PI3K may interact with the phosphotyrosine sequence of RTK, which may further activate PI3K [52], it could be suggested that RTK contains a target sequence at its extracellular domain, which may be recognized by the ALS IgG. Nevertheless, the nature of the epitope for ALS IgG remains elusive, even though different candidates were recognized in distinct cells such as neurofilaments [55], ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) [56], N-type calcium channel [14], L-type calcium channel [57], and Fas (APO-1, CD95), a member of the tumor necrosis factor receptor family [58]. Such diversity of potential epitopes is consistent with the notion that ALS is a multifocal disease, where several targets for the immune/inflammatory response may exist in the brain in addition to motor neurons.…”

Neurofilament Subunit L Levels in the Cerebrospinal Fluid and Serum of Patients with Amyotrophic Lateral Sclerosis

“…Moreover, the permeability of the blood-brain barrier is a factors that affect the redistribution of NFs. Some studies suggest that antibody clearance may be another way to balance NF-L levels [17], ultimately resulting in a flat NF-L concentration profile, both in the CSF and the serum.…”