Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis.
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.
Kolln
Johanna
J
Department of Neurology, University of California, Irvine, CA 92697, USA.
Ren
Hui-Min
HM
Da
Reng-Rong
RR
Zhang
Yiping
Y
Spillner
Edzard
E
Olek
Michael
M
Hermanowicz
Neal
N
Hilgenberg
Lutz G
LG
Smith
Martin A
MA
van den Noort
Stanley
S
Qin
Yufen
Y
D000328:Adult; D001323:Autoantibodies / Q000032:analysis / Q000134:cerebrospinal fluid*; D001324:Autoantigens; D001369:Axons / Q000276:immunology; D001402:B-Lymphocytes; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D009422:Nervous System Diseases / Q000276:immunology; D009474:Neurons / Q000276:immunology; D014305:Triose-Phosphate Isomerase / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D014305:Triose-Phosphate Isomerase