Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS)

摘要

Aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is still a mystery. Among several hypotheses autoimmune mechanisms are also taken into account. We report here our investigations of auto-antibodies against proteins of spinal cord cells in the cerebrospinal fluid (CSF) and serum of ALS patients. The results were correlated with the severity of disease course. The subjects were 57 ALS patients (29 severe, 28 mild) and 10 normal controls. The major finding in CSF was the presence of antibodies against a 70 kD protein in the majority of ALS patients. This protein was identified as neurofilament 68. The second protein of high reactivity and frequency of appearance was a 82 kD protein, which was identified as a-actinin. Less reactive and less frequent were antibodies directed against 55 kD and 40 kD proteins. They were immunologically defined to be related to desmin and actin, resp. The difference between the reactivity of anti-neurofilament and anti-desmin related protein in the severe and mild ALS groups was significant. More frequent were the anti-neurofilament antibodies in the severe ALS cases as compared to the milder ones. In normal CSF, antibodies directed against 55 kD, 70 kD and 82 kD proteins were present in traces and appeared in 5%, 20% and 10% of cases, respectively. In the serum of 30% of severe ALS patients traces of antibodies against 70 kD protein were detected. The morphological studies in the presence of CSF of ALS patients revealed pronounced immunoreactivity of spinal cord neurons, mainly within anterior horns. The significance of the presence of auto-antibodies in CSF of ALS patients against cellular proteins of the spinal cord is hard to define. It is conceivable that they appear as a secondary immunological consequence of neuronal death. It is also possible that they may accelerate the course of neuronal degeneration.