Journal
JOURNAL OF AUTOIMMUNITY
Volume 32, Issue 1, Pages 24-32Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2008.10.002
Keywords
Cerebrospinal fluid; GAD65; T cell; Stiff person syndrome
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Most patients with stiff person syndrome (SPS) display intrathecal synthesis of oligoclonal and high-avidity IgG against the 65 kDa isoform of glutamic acid decarboxylase (GAD65 IgG), but little is known about the mechanisms driving this immune response. We hypothesized that GAD65-specific T cells accumulating in the central nervous system drive the intrathecal GAD65 IgG production. Accordingly, we were able to clone HLA-DR or DP restricted GAD65-specific T cells from the cerebrospinal fluid (CSF) of all three patients with. but not in one patient without substantial intrathecal production of GAD65 IgG. The CSFT cells recognized four GAD65 epitopes,which were unique to each patient. In two patients, identical or closely related GAD65-specific CSF T cell clones were expanded in vivo. In contrast to the findings in CSF, only one GAD65-specific T cell clone could be raised from the blood of one single patient. Cysteine in amino acid position 474, which is important for enzymatic function of GAD65, was critical for recognition of GAD65(474-484) by HLA-DP restricted CSF T cells. We conclude that GAD65-specific T cells and clonally expanded GAD65-specific B cells coexist intrathecally, where they may collaborate in the synthesis of GAD65 IgG. (C) 2008 Elsevier Ltd. All rights reserved.
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