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* Department of Neurology and
Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697; and
Department of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To study the axonal Ags involved in MS, we identified the glycolytic enzymes, triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs generated from clonal B cells in the CSF and in lesions from MS patients. Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%), clinically isolated syndrome (CIS) suggestive of MS (40%), other inflammatory neurological diseases (OIND; 29%), and other noninflammatory neurological diseases (ONIND; 31%). Levels of GAPDH-reactive Abs were elevated in MS patients (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%). The coexistence of both autoantibodies was detected in 10 MS patients (29%), and 1 CIS patient (3%), but not in patients with OIND/ONIND. Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively. The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Multiple Sclerosis Society Grant RG 3156A1/1 and National Institutes of Health Grant RO1 NS40534-01A1.
2 J.K. and H.-M.R. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Yufen Qin, Department of Neurology, University of California, 100 Irvine Hall, Irvine, CA 92697. E-mail address: qiny{at}uci.edu
4 Abbreviations used in this paper: MS, multiple sclerosis; CIS, clinically isolated syndrome; CSF, cerebrospinal fluid; scFv, single chain variable fragment; NAWM, normal appearing white matter; TPI, triosephosphate isomerase; OIND, other inflammatory neurological disease; ONIND, other noninflammatory neurological disease; RT, room temperature.
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