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From the Department of Biological Chemistry (S. Halev, D. Orion, and Dr. Atlas), Institute of Life Sciences, The Hebrew University of Jerusalem; and the Department of Neurology (Drs. Offen, Mosberg, Stern-Goldberg, and Melamed), Rabin Medical Center-Beilinson Campus, Sackler School of Medicine, Tel-Aviv University, Petah-Tikva, Israel.
Address correspondence and reprint requests to Dr. Daphne Atlas, The Hebrew University of Jerusalem, Department of Biological Chemistry, Institute of Life Sciences, Jerusalem, 91904 Israel.
Objective: To examine the presence of anti-L-type calcium channel antibodies 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 sporadic ALS contain antibodies against voltagegated calcium channels (L-type and P-type), but others do not support these findings.
Methods: Regulated secretion of tritiated dopamine ([3H]DA) in PC12 cells in mediated exclusively by calcium entry through L-type calcium channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [3H]DA release by interfering with calcium entry through L-type calcium channels, evoked release in PC12 cells was determined in the presence of 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 [3H]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 inhibition by ALS IgG correlated positively with disease duration (r = 0.68; 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.
*These authors contributed equally to this article.
Supported in part by the H.L. Lauterbach Fund in a grant to D.A.
Received November 26, 1997. Accepted in final form June 6, 1998.
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