Proteolytic activity in amyotrophic lateral sclerosis IgG preparations

Annals of Neurology
O Nyormoi

Abstract

Sporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltage-gated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the binding of 8B7 monoclonal antibody to the alpha1 subunit of voltage-gated calcium channels, suggesting overlapping epitopes of the two antibodies. It is, however, possible that the 8B7 epitope was destroyed by proteases. Data presented here show that the blocking of 8B7 binding to the alpha1 subunit by diethylaminoethyl cellulose (DEAE)-purified amyotrophic lateral sclerosis IgG was not observed with Fab fragments of amyotrophic lateral sclerosis IgG. The blocking was prevented by serine protease inhibitors. Moreover, it was reproduced by plasminogen and urokinase. These observations suggest that raised proteolytic activity in amyotrophic lateral sclerosis IgG preparations may be responsible for the blockade of 8B7 monoclonal antibody demonstrated previously. They also indicate the need to be particularly cautious when interpreting the results of incubation in amyotrophic lateral sclerosis sera or IgG preparations...Continue Reading

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Citations

Oct 23, 1997·Annals of Neurology·D A Greenberg
Jul 10, 1999·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·A SchmiedJ P Vedel
Nov 23, 2012·Journal of Clinical Neuromuscular Disease·Raja MehannaYadollah Harati
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Jun 26, 2008·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Bin LiChun-Yan Li

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