Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Identification of autoantibody epitopes of glutamic acid decarboxylase in Stiff-man syndrome patients

Li, L. ; Hagopian, W. A. ; Brashear, H. R. ; Daniels, T. and Lernmark, A. LU orcid (1994) In Journal of Immunology 152(2). p.930-934
Abstract

Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter γ- aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera from two patients with SMS was used in an immunoblotting assay with recombinant GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can recognize specific epitopes. We found that both SMS sera recognized the GAD65, but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block the autoantibodies, two GAD65... (More)

Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter γ- aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera from two patients with SMS was used in an immunoblotting assay with recombinant GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can recognize specific epitopes. We found that both SMS sera recognized the GAD65, but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block the autoantibodies, two GAD65 epitopes were identified. One epitope recognized by both patients' sera, was blocked by the peptide representing amino acid residues 354-368. In one patient only, blocking was also observed by a peptide representing residues 390-402, which includes the binding site of the GAD cofactor, pyridoxal 5'-phosphate. A single amino acid substitution in GAD65 at position 401 (leucine to proline) and representing the analogous GAD67 sequence in this region significantly reduced the peptide's inhibitory effect. These findings suggest that SMS GAD autoantibodies share distinct GAD65 linear epitopes and that some SMS patients' autoantibodies may block the active site, explaining SMS GABA deficiency.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Journal of Immunology
volume
152
issue
2
pages
930 - 934
publisher
American Association of Immunologists
external identifiers
  • scopus:0028267951
  • pmid:7506741
ISSN
0022-1767
language
English
LU publication?
no
id
018e10b9-8d61-4224-a0c9-53422b56c4ae
alternative location
https://www.jimmunol.org/content/jimmunol/152/2/930.full.pdf
date added to LUP
2019-09-11 09:05:51
date last changed
2024-03-13 08:10:43
@article{018e10b9-8d61-4224-a0c9-53422b56c4ae,
  abstract     = {{<p>Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter γ- aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera from two patients with SMS was used in an immunoblotting assay with recombinant GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can recognize specific epitopes. We found that both SMS sera recognized the GAD65, but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block the autoantibodies, two GAD65 epitopes were identified. One epitope recognized by both patients' sera, was blocked by the peptide representing amino acid residues 354-368. In one patient only, blocking was also observed by a peptide representing residues 390-402, which includes the binding site of the GAD cofactor, pyridoxal 5'-phosphate. A single amino acid substitution in GAD65 at position 401 (leucine to proline) and representing the analogous GAD67 sequence in this region significantly reduced the peptide's inhibitory effect. These findings suggest that SMS GAD autoantibodies share distinct GAD65 linear epitopes and that some SMS patients' autoantibodies may block the active site, explaining SMS GABA deficiency.</p>}},
  author       = {{Li, L. and Hagopian, W. A. and Brashear, H. R. and Daniels, T. and Lernmark, A.}},
  issn         = {{0022-1767}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{930--934}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{Identification of autoantibody epitopes of glutamic acid decarboxylase in Stiff-man syndrome patients}},
  url          = {{https://www.jimmunol.org/content/jimmunol/152/2/930.full.pdf}},
  volume       = {{152}},
  year         = {{1994}},
}