Anti-neural antibodies in serum and cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients

Abstract

Objectives ‐ An autoimmune basis has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). This hypothesis is supported by the presence of antibodies that interact with motoneuron antigens in serum of these patients. Against autoimmunity are the discrepances in the frequency of the antibodies appearance and also failure of immunosuppression. The aim of our study was to evaluate the titer of antibodies against GM1‐gangliosides, AGM1‐gangliosides and anti‐sulfatides in paired serum and cerebrospinal fluid samples in the ALS patients. Material and methods ‐ Serum of 103 and CSF of 79 patients with ALS was examined. The “disease controls” consisted of 22 cases of other motor neuron diseases and 50 healthy, age‐matched normals. CSF was drawn at the same time from 79 ALS patients, 6 cases of the “disease controls” and 50 normals. To study the titer of antibodies against GM1‐gangliosides, AGM1‐gangliosides and sulfatides the ELISA technique has been applied. Results ‐ An increased titer against GM1‐gangliosides, AGM1‐gangliosides and sulfatides in ALS appeared in serum in 18%, 32% and 11%, resp., in the “disease controls” the increased antibodies titer appeared in single cases. In CSF the appropriate values in ALS were 20%, 15%, 8%, resp. In the “disease controls” a high antibodies titer was a rare finding. Conclusions ‐ It is concluded that in some ALS cases and also in some patients with other motor neuron diseases an autoimmune mechanism may contribute to motor neuron injury.

CSF markers in amyotrophic lateral sclerosis

“…Detoxification of hydrogen peroxide (Tohgi et al 1999) Nitrate (NO3 -) $ Nitric oxide bio-transformation (Pirttilä et al 2004) Free iron $ A radical generator (Kokić et al 2005) Biomarkers of the neurotransmission Glutamate : Excitotoxicity (Niebroj-Dobosz et al 1999;SpreuxVaroquaux et al 2002;Zhao et al 2004) Amino acids (i.e., aspartate, glycine)…”

“…$ Excitotoxicity (Niebroj-Dobosz et al 1999) Markers of the neuroprotection Pigment epithelium-derived factor (PEDF)…”

Aberrant Control of Motoneuronal Excitability in Amyotrophic Lateral Sclerosis: Excitatory Glutamate / D‐Serine vs. Inhibitory Glycine/γ‐Aminobutanoic Acid (GABA)

“…The reports that inhibitory synaptic boutons dominate excitatory ones in spinal motoneurons [27] and they express high levels of glycine and GABA A receptors indicate that inhibitory neurotransmission plays a considerable role in modulating motoneuronal excitability and firing rates [28]. An imbalance in the levels of excitatory and inhibitory synaptic transmission in ALS was hypothesized [109], and an involvement of inhibitory neurotransmitter has been supported by studies of ALS patients: abnormal GABA and glycine levels were observed in serum of ALS patients [110]; levels of glycine were decreased in autopsy spinal cords of ALS patients [111]; intra-cortical inhibition was impaired in living patients with ALS [112]. As for the receptors of inhibitory neurotransmitters, expression of GABA A receptor is speculated to decrease in motor cortex and spinal cord of ALS patients shown by the reduced binding of a GABA ligand and mRNA expression [113 -116] but be unchanged in lower motor neurons of a mSOD1 mouse model [117] [118].…”

Aluminum?s Role in CNS-immune System Interactions leading to Neurological Disorders

“…Although space precludes a full description of the literature, there is now abundant evidence for an autoimmune component to the classical age-related neurological diseases, including ALS [23][24][25][26][27], Alzheimer's [25,[28][29][30][31][32] and Parkinson's diseases [28]. It remains, however, uncertain whether the immune markers found in affected regions of the CNS are causal or secondary to the resulting loss of neurons [23][24][25][26][27][28][29][30][31][32].…”

“…It remains, however, uncertain whether the immune markers found in affected regions of the CNS are causal or secondary to the resulting loss of neurons [23][24][25][26][27][28][29][30][31][32]. This same consideration applies to the typical presence of activated microglia at the site of most CNS lesions and whether the neuroinflammatory response is primary or secondary to neuronal degeneration.…”