Comparison between cerebrospinal fluid and serum levels of myelin-associated glycoprotein, total antioxidant capacity, and 8-hydroxy-2'-deoxyguanosine in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelinated lesions in the brain, the spinal cord, and the optic nerve. It is one of the most common neurological disorders. In this study, serum and cerebrospinal fluid (CSF) levels of total antioxidant capacity (TAC), myelin-associated glycoprotein (MAG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated to determine their effects on MS. MATERIALS AND METHOD: In this study, 25 serum and cerebrospinal samples from MS patients as a case group and 40 serum and CSF samples from healthy participants as a control group were collected and analyzed. Concentrations of TAC, MAG, and 8-OhdG were determined in the samples using a dedicated kit and relayed using the ELISA device. RESULTS: The mean serum antibody levels of MAG and TAC were higher in the case group than the control group, although the difference in the MAG level was not significant (P > 0.05). However, the mean serum level of -8 OHdG was lower in the case group than the control group. Moreover, the mean levels of the evaluated biomarkers in the CSF samples were higher in the case group than in the control group. Still, the difference was only significant in terms of TAC levels (P < 0.05). Receiver operating characteristics curve analysis showed that the area under the curve was 0.71 and 0.69 for 8-OhdG and TAC serum levels, respectively, and 0.73 for both TAC and CSF levels, which was not significantly different from that in other biomarkers. CONCLUSION: Elevated TAC levels in serum and CSF samples and 8-OhdG in serum samples may be associated with MS pathogenesis. However, further investigation is needed to consider these cases as a follow-up to the therapeutic goals or treatment process.

Anti-myelin associated glycoprotein antibodies recognize HNK-1 epitope on CNS.

Antibodies to myelin-associated glycoprotein (MAG) are associated with demyelinating polyneuropathy and are specific for the HNK-1 epitope. To test if anti-MAG IgM recognize HNK-1 on CNS, sera from 20 patients and 238 controls were tested on rat slices by indirect immunofluorescence (IIF). IgM from anti-MAG positive patients, but not from control sera, stained rat brain with perineuronal or neuropil pattern, depending on the CNS region. IIF titers significantly correlated with ELISA anti-MAG titers. The staining of patients' sera were inhibited by mouse anti-HNK-1 monoclonal antibody. Our results demonstrate that anti-MAG IgM recognizes HNK-1 outside the peripheral nerve myelin carriers.

Elevated intrathecal myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis.

OBJECTIVE: To evaluate antibodies to myelin oligodendrocyte glycoprotein (MOG) in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and control individuals. DESIGN: Prospective case-control series. SETTING: Academic referral center. PATIENTS: Twenty-six controls with noninflammatory neurologic disease and 35 patients with MS donated serum and CSF for recombinant MOG (rMOG) antibody determination. MAIN OUTCOME MEASURES: Serum and CSF rMOG antibody and albumin levels were used to calculate an rMOG index. Clinical disability, CSF markers, and magnetic resonance metrics were correlated with the rMOG index. RESULTS: The rMOG index was elevated in MS patients compared with controls (P = .01). Patients with progressive MS exhibited elevated rMOG indexes compared with patients with relapsing-remitting MS (P = .04). The rMOG index was inferior to the IgG index in differentiating MS patients from controls. However, 7 of 16 patients with MS who had normal immunoglobulin G indexes had an elevated rMOG index. The rMOG index did not correlate with clinical disability, other CSF markers, or radiographic outcome measures. CONCLUSIONS: The rMOG index, a marker of intrathecal MOG antibody production, may provide complementary information to routine CSF testing in the diagnosis of MS. Furthermore, intrathecal anti-MOG antibody production may be more pronounced in progressive than in relapsing forms of MS.

Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein.

Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading.

Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis.

OBJECTIVE: To evaluate the presence and specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. SETTING: Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES: Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P = .005 and P = .03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti-MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs (P = .003 for both comparisons) and with controls (P = .03 and P = .04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82, respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.