Objective: To examine the presence of anti-L-type calcium channel anti
bodies in the serum of ALS patients. Background: Autoimmunity has been
hypothesized as one of the mechanisms underlying the pathogenesis of
sporadic ALS. Previous studies reported that sera from patients with s
poradic ALS contain antibodies against voltage-gated calcium channels
(L-type and P-type), but others do not support these findings. Methods
: Regulated secretion of tritiated dopamine ([H-3]DA) in PC12 cells is
mediated exclusively by calcium entry through L-type calcium channels
. To examine whether purified ALS immunoglobulin G (IgG) inhibits [H-3
]DA release by interfering with calcium entry through L-type calcium c
hannels, evoked release in PC12 cells was determined in the presence o
f ALS IgG. This functional assay provides a sensitive way to examine L
-type calcium channel interaction with IgG from ALS patients. Results:
A significant inhibition of depolarization-evoked [H-3]DA release (32
+/- 4%) was observed by purified IgG from ALS patients compared with
control subjects (11 +/- 2%; p < 0.01). Significant inhibition by IgG
occurred in 79% (15/19) of the ALS patients compared with only 29% (5/
17) in the control group (p < 0.01). The level of calcium channel inhi
bition by ALS IgG correlated positively with disease duration (r = 0.6
8; p < 0.01) and correlated negatively with age (r = -0.48; p < 0.05).
Conclusions: These results confirm the presence of antibodies against
the L-type calcium channel in the majority of sera from ALS patients,
supporting their role in the pathogenesis of ALS.