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

J Neurosci. 2002 Jan 1;22(1):123-32. doi: 10.1523/JNEUROSCI.22-01-00123.2002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity
  • Autoantibodies / blood*
  • Autoantibodies / cerebrospinal fluid
  • Autoantibodies / pharmacology
  • Biomarkers / blood
  • Cysteine / analogs & derivatives*
  • Cysteine / antagonists & inhibitors
  • Cysteine / immunology*
  • Demyelinating Diseases / blood
  • Demyelinating Diseases / diagnosis*
  • Demyelinating Diseases / etiology
  • Disease Models, Animal
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / blood*
  • Encephalomyelitis, Autoimmune, Experimental / complications
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Humans
  • Immunoglobulin M / blood
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / 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
  • S-Nitrosothiols / immunology*
  • Serum Albumin, Bovine / immunology
  • Spinal Cord / pathology


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