Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis.

Abstract

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.

• Authors: Anne I Boullerne, Jose J Rodriguez, Tarik Touil, Bruno Brochet, Stephan Schmidt, Nora D Abrous, Michel Le Moal, Jeffrey R Pua, Mark A Jensen, Willy Mayo, Barry G W Arnason, Klaus G Petry
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 22 Issue 1 Pg. 123-32 (Jan 01 2002) ISSN: 1529-2401 [Electronic] United States
• PMID: 11756495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Biomarkers
• Immunoglobulin M
• Myelin Basic Protein
• Nitroso Compounds
• Peptide Fragments
• S-Nitrosothiols
• S-nitrosoalbumin
• Serum Albumin, Bovine
• S-nitrosocysteine
• Cysteine

Topics

• Animals
• Antibody Specificity
• Autoantibodies (blood, cerebrospinal fluid, pharmacology)
• Biomarkers (blood)
• Cysteine (analogs & derivatives, antagonists & inhibitors, immunology)
• Demyelinating Diseases (blood, diagnosis, etiology)
• Disease Models, Animal
• Disease Progression
• Encephalomyelitis, Autoimmune, Experimental (blood, complications, immunology, pathology)
• Female
• Humans
• Immunoglobulin M (blood)
• Multiple Sclerosis (blood, diagnosis, immunology)
• Myelin Basic Protein (immunology)
• Nitroso Compounds
• Peptide Fragments (immunology)
• Predictive Value of Tests
• Rats
• Rats, Inbred Lew
• Recurrence
• Remission, Spontaneous
• S-Nitrosothiols (antagonists & inhibitors, immunology)
• Serum Albumin, Bovine (immunology)
• Spinal Cord (pathology)