Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis.
Multiple sclerosis (MS) is characterized by inflammation within the CNS. This inflammatory response is associated with production of nitric oxide (NO) and NO-related species that nitrosylate thiols. We postulated that MS patients would exhibit an antibody (Ab) response directed against proteins containing S-nitrosocysteine (SNO-cysteine) and showed that anti-NO-cysteine Abs of the IgM isotype are in fact present in the sera of some MS patients (Boullerne et al., 1995). We report here the presence of a seemingly identical Ab response directed against SNO-cysteine in an acute model of MS, experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats with the 68-84 peptide of guinea pig myelin basic protein (MBP(68-84)). Serum levels of anti-SNO-cysteine Abs peaked 1 week before the onset of clinical signs and well before the appearance of anti-MBP(68-84) Abs. The anti-SNO-cysteine Ab peak titer correlated with the extent of subsequent CNS demyelination, suggesting a link between Ab level and CNS lesion formation. In relapsing-remitting MS patients, we found elevated anti-SNO-cysteine Ab at times of relapse and normal values in most patients judged to be in remission. Two-thirds of patients with secondary progressive MS had elevated anti-SNO-cysteine Ab levels, including those receiving interferon beta-1b. The data show that a rise in circulating anti-SNO-cysteine Ab levels precedes onset of EAE. Anti-SNO-cysteine Abs are also elevated at times of MS attacks and in progressive disease, suggesting a possible role for these Abs, measurable in blood, as a biological marker for clinical activity.
Boullerne
Anne I
AI
Department of Neurology, University of Chicago, Chicago, Illinois 60637, USA. abouller@neurology.bsd.uchicago.edu
Rodriguez
Jose J
JJ
Touil
Tarik
T
Brochet
Bruno
B
Schmidt
Stephan
S
Abrous
Nora D
ND
Le Moal
Michel
M
Pua
Jeffrey R
JR
Jensen
Mark A
MA
Mayo
Willy
W
Arnason
Barry G W
BG
Petry
Klaus G
KG
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D003545:Cysteine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000276:immunology*; D003711:Demyelinating Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D009603:Nitroso Compounds; D010446:Peptide Fragments / Q000276:immunology; D011237:Predictive Value of Tests; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D012075:Remission, Spontaneous; D026403:S-Nitrosothiols / Q000037:antagonists & inhibitors / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology
D001323:Autoantibodies; D015415:Biomarkers; D007075:Immunoglobulin M; D004676:Myelin Basic Protein; D009603:Nitroso Compounds; D010446:Peptide Fragments; D026403:S-Nitrosothiols; C091665:S-nitrosoalbumin; D012710:Serum Albumin, Bovine; C021315:S-nitrosocysteine; D003545:Cysteine