anti-MOG IgG Research Articles

Myelin oligodendrocyte glycoprotein antibodies and multiple sclerosis in healthy young adults

It remains uncertain whether the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in healthy individuals contributes to predict their risk of developing multiple sclerosis (MS). Prospective, nested case-control study of more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. A total of 126 MS cases and 252 controls matched by age, sex, race/ethnicity, and dates of blood collection were included in the analysis. An ELISA was used to detect IgM and IgG antibodies to MOG. Analyses were conducted with and without adjustment for serum titers of antibodies to the Epstein-Barr nuclear antigen (EBNA), which are an established risk factor for MS. The presence of anti-MOG IgG antibodies in serum was associated with an increase in risk of developing MS (relative risk for anti-MOG IgG+/IgM- vs seronegativity to both anti-MOG IgM and IgG: 2.03; 95% CI: 1.19-3.46; p = 0.01). This association, however, was attenuated and no longer significant after adjustment for titers of antibodies to EBNA, which were higher among individuals positive for anti-MOG antibodies. Our findings suggest that although individuals with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have an increased risk of developing multiple sclerosis, this association may at least in part reflect cross-reactivity between MOG and Epstein-Barr nuclear antigen.

Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis

Patients with a single episode of neurologic dysfunction and brain magnetic resonance imaging (MRI) scans suggestive of multiple sclerosis are at high risk for clinically definite multiple sclerosis, but the outcome for individual patients is unpredictable. An increased risk of progression to clinically definite multiple sclerosis in patients with serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) has been reported. We measured serum anti-MOG and anti-MBP IgG and IgM antibodies in 462 patients with a first clinical event suggestive of multiple sclerosis and at least two clinically silent lesions on brain MRI. The patients were participating in a multicenter trial of treatment with interferon beta-1b. Antibodies were assessed by Western blot analysis at baseline, and the results compared with the time and rate of progression to clinically definite multiple sclerosis or a diagnosis of multiple sclerosis as defined by an international panel (the McDonald criteria). Regular visits were scheduled for the assessment of neurologic impairment and for MRI before treatment and at months 3, 6, 9, 12, 18, and 24. No associations were found between the presence of anti-MOG and anti-MBP IgM and IgG antibodies and progression to clinically definite multiple sclerosis or a diagnosis of multiple sclerosis according to the McDonald criteria, either in the entire cohort or in any subgroups of the study population. Serum antibodies against MOG and MBP, as detected by Western blot analysis, are not associated with an increased risk of progression to clinically definite multiple sclerosis in patients who have had a clinically isolated syndrome suggestive of multiple sclerosis.

Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis

Objective Myelin oligodendrocyte glycoprotein (MOG) is a highly immunogenic minor component on the outside surface of CNS myelin which is believed to be one of the autoantigens in multiple sclerosis. The aim of this study was to evaluate the diagnostic potential of anti-MOG IgG antibody levels in cerebrospinal fluid (CSF) and serum of patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and non-inflammatory neurological diseases (NIND) as markers for the different clinical types of multiple sclerosis. Patients and methods Consecutive serum and cerebrospinal fluid samples were taken from 21 patients with RRMS, 7 patients with PPMS and 19 patients with NIND. The antibody responses to MOG were determined in paired samples of these differrent clinical groups by enzyme-linked immunoassay using a recombinant human MOG protein. Results The performed analysis indicated that the differences in levels of anti-MOG IgG antibody in serum and cerebrospinal fluid from the patients with RRMS, PPMS or NIND were not statistically significant. Conclusion The assay is not sensitive or specific enough to be used as a differential diagnostic tool for the clinical types of MS, nor for MS itself.

Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects.

The authors used a liquid-phase radiobinding assay to measure serum anti-myelin oligodendrocyte protein (MOG) immunoglobulin (Ig) G in 87 patients with multiple sclerosis (MS), in 12 patients with encephalomyelitis, and in 47 healthy subjects. Anti-MOG IgM was determined in samples obtained at onset from 40 of 87 patients with MS and in control subjects. The frequency of positive samples with low titers of anti-MOG IgG (< or =5.7%) and IgM (< or =8.3%) was similar in all the groups and subgroups. Binding competition experiments showed that these antibodies had low affinity. Anti-MOG antibodies are not disease specific.

Gender does not influence the susceptibility of C57BL/6 mice to develop chronic experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), is more prevalent in females than males. It is well documented that a significant gender difference exits in the susceptibility of mice to develop experimental autoimmune encephalomyelitis (EAE), a model of MS, induced by myelin basic protein or proteolipid protein. In contrast, we report here that no significant difference between female mice and male mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE was observed in the incidence of disease, clinical course, histological findings in the CNS, T cell response and cytokine production of spleen cells to MOG, and anti-MOG IgG level in serum. These results suggest that gender-related difference in EAE depends on the encephalitogen and/or the strain of animals used. Given that MOG is a putative pathogenic myelin antigen in MS, the present findings may have implications for the pathogenesis of this disease.

Prevention of Experimental Autoimmune Encephalomyelitis in the Common Marmoset (Callithrix jacchus) Using a Chimeric Antagonist Monoclonal Antibody Against Human CD40 Is Associated with Altered B Cell Responses

Inhibition of CD40-CD40 ligand interaction is a potentially effective approach for treatment of autoimmune diseases, such as multiple sclerosis. We have investigated this concept with a chimeric antagonist anti-human CD40 mAb (ch5D12) in the marmoset monkey experimental autoimmune encephalomyelitis (EAE) model. Marmosets were immunized with recombinant human myelin oligodendrocyte glycoprotein (rMOG) and treated from the day before immunization (day -1) until day 50 with either ch5D12 (5 mg/kg every 2-4 days) or placebo. On day 41 after the induction of EAE, four of four placebo-treated monkeys had developed severe clinical EAE, whereas all animals from the ch5D12-treated group were completely free of disease symptoms. High serum levels of ch5D12 associated with complete coating of CD40 on circulating B cells were found. At necropsy placebo- and ch5D12-treated animals showed similar MOG-specific lymphoproliferative responses in vitro, but ch5D12 treatment resulted in strongly reduced anti-MOG IgM Ab responses and delayed anti-MOG IgG responses. Most importantly, treatment with ch5D12 prevented intramolecular spreading of epitope recognition. Postmortem magnetic resonance imaging and immunohistologic analysis of the CNS showed a markedly reduced lesion load after ch5D12 treatment. In conclusion, the strong reduction of clinical, pathological, and radiological aspects of EAE by ch5D12 treatment in this preclinical model points to a therapeutic potential of this engineered antagonist anti-CD40 mAb for multiple sclerosis.

T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS.

Antibodies to myelin-oligodendrocyte glycoprotein in cerebrospinal fluid from patients with multiple sclerosis and controls

Myelin-oligodendrocyte glycoprotein (MOG) has been implicated as a target for antibody-mediated immune attack in experimental autoimmune encephalomyelitis (EAE) which has been used extensively as an experimental model of multiple sclerosis (MS). We have screened cerebrospinal fluid (CSF) and plasma from 30 patients with MS, 30 with other neurological diseases (OND) and 30 with tension headache for anti-MOG antibodies of IgG isotype by enzyme-linked immunosorbent assay (ELISA). Such antibodies were detected in CSF from seven of the patients with MS, compared to two with OND and one with tension headache. No anti-MOG IgG antibodies were demonstrable in plasma. Antibody specificity was confirmed by Western blot immunostaining. Antibody levels were higher in MS compared to OND and tension headache. No correlation was observed between anti-MOG IgG antibodies and total IgG levels in CSF. The significance of anti-MOG antibodies demonstrated in MS CSF remains to be defined.