AUTOIMMUNITY AND ALS

Significant evidence has accrued suggesting that antibodies to voltage -gated calcium channel are observed in at least some patients with spo radic ALS (SALS) and that such antibodies alter the function of these ion channels in vitro and in vivo. Further, passive transfer of these immunoglobulin-containing fractions into mice produces changes at the neuromuscular junction that are very similar to changes observed in pa tients with SALS. These changes reflect local alterations in intracell ular Ca2+ homeostasis and, in animal models, may also evidence early c hanges of motoneuron injury, such as Golgi apparatus swelling and frag mentation. Although not yet documented to induce motoneuron death in v ivo, SALS immunoglobulins induce Ca2+-dependent apoptosis in a differe ntiated motoneuron hybrid cell line via a mechanism that involves oxid ative injury. SALS immunoglobulin-mediated apoptosis in these cells is regulated by the presence of the same calcium-binding proteins that m ay modulate selective motoneuron vulnerability in SALS.