Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of the motor neurons leading to muscle weakness, increasing disability and death of affected individuals. Several pathogenic hypotheses have been proposed to explain the selective motor neurons degeneration: excitotoxicity, oxidative stress and autoimmunity. Many data from autoptic spinal cord material and blood examination of the ALS patients support an immune system involvement. Primarily, inflammatory foci have been found in ALS patients’ spinal cord, by using a panel of monoclonal antibodies to characterize different leukocyte subsets (Engelhardt et al., 1993; Troost et al., 1990).
T-helper cells have been observed in proximity of degenerating corticospinal tracts; Thelper and T-suppressor cells, with a variable number of macrophages, have been found in ventral horns (Troost et al., 1990). No infiltrating B-cells have been found. Alterations of total lymphocyte count (Provinciali et al., 1988; Tavolato et al., 1975) and T subset distribution (Westall et al., 1983) have been reported.
In addition, increased blood IgG levels have been found in ALS patients (Duarte et al., 1991).
Serum immunoglobulins from ALS patients showed enhanced in vitro binding to rat spinal cord cells (Digby et al., 1985) and were cytotoxicwhen added to a motor neuron cell culture (Alexianu et al., 1994; Demestre et al., 2005). Moreover, IgG deposits have been demonstrated in motor cortex and spinal cord sections, and in motor neurons from ALS patients (Donnenfeld et al., 1984; Engelhardt and Appel, 1990; Fishman and Drachman, 1995). Different serum IgM antibodies such as those anti-voltage-gated Ca2+ channel (Kimura et al., 1994; Smith et al., 1992), anti-gangliosideGM1 (Li and Pestronk, 1991), anti-sulfoglucuronyl paragloboside (Younes-Chennoufi et al., 1995), anti-neurofilaments (Couratier et al., 1998) and anti-Fas (Sengun andAppel, 2003;Yi et al., 2000) have been identified in ALS patients.
Furthermore, high cytokine levels have been described in plasma from ALS patients and sometimes correlated with the clinical status. Transforming Growth Factor (TGF)-beta 1 concentration was significantly higher in sera from ALS patients at terminal state than in controls (Ilzecka et al., 2002). Abnormal Interleukin 6 (IL-6) amounts have been found in sera and CSF from ALS patients, and they have been related to hypoxemia severity (Moreau et al., 2005). Finally, antigenic Tumor Necrosis Factor (TNF) and its soluble receptors (sTNF-Rs) were significantly higher in plasmas of ALS patients than in those of healthy controls (Poloni et al., 2000).