Marmoset Fine B Cell and T Cell Epitope Specificities Mapped onto a Homology Model of the Extracellular Domain of Human Myelin Oligodendrocyte Glycoprotein

Mesleh, Michael F.; Belmar, Nicole A.; Lu, Chuan Wei; Krishnan, Viswanathan V; Maxwell, Robert S.; Genain, Claude P.; Cosman, Monique

doi:10.1006/nbdi.2001.0474

Cited by 23 publications

(10 citation statements)

References 62 publications

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“…This is probably because of the fact that most detection methods focus on reactivity to a single myelin protein whereas anti-myelin antibody responses in MS patients are very heterogeneous with respect to their specificities 21. Moreover, relevant antibodies may only be detected by methods that use conformational post-translationally modified myelin epitopes whereas most methods use denaturated or recombinant myelin proteins 13 18 19. Here we used a novel flow cytometry based assay that detects antibody reactivity to myelin particles, allowing the simultaneous detection of a wide variety of myelin protein and lipid specific antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant, in vitro translated and native purified myelin proteins have been used for detection of myelin specific antibodies 13 18 19 20. None of these methods takes into account the specific structure of folded myelin proteins in association with a hydrophobic, lipid-rich bilayer membrane as they are displayed to the immune system in vivo on myelin sheaths.…”

mentioning

confidence: 99%

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Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis

Vogt

Teunissen

Iacobaeus

et al. 2008

Journal of Neurology, Neurosurgery & Psychiatry

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Objective: Recent studies reported contrasting results with respect to the presence of anti-myelin protein antibodies in multiple sclerosis (MS) and their relation with disease activity. This may be due to the heterogeneous specificity of autoantibodies in MS and the inability of most methods to detect pathogenically relevant antibodies. Here, myelin particles were used to detect anti-myelin antibodies in the CSF of MS patients. Subsequently, their relation with MRI parameters was evaluated. Methods: Anti-myelin IgG antibody reactivity was determined in the CSF of patients with MS (n = 65) and clinically isolated syndrome (CIS, n = 37) using a novel flow cytometry based assay. In addition, the CSF of patients with other neurological diseases (OND, n = 17), inflammatory neurological diseases (IND, n = 33) and controls (n = 22) was tested. Results: Compared with controls, increased anti-myelin IgG antibody reactivity was most frequently found in the CSF of patients with CIS (46%, p = 0.002), relapsingremitting MS (56%, p,0.001) and secondary progressive MS (55%, p,0.001), together constituting 85% of all positive CSF samples. In contrast, elevated anti-myelin IgG antibody reactivity was present in a minority of IND patients (21%), marginally present in controls (5%) and absent in OND patients (0%). Most strikingly, anti-myelin IgG antibody reactivity was related to the number of T2 lesions (r = 0.31, p = 0.041) and gadolinium enhancing T1 lesions (r = 0.37, p = 0.016) on brain MRI in CIS and relapse onset MS patients. Conclusion: CSF anti-myelin IgG antibodies are promising specific biomarkers in CIS and relapse onset MS and correlate with MR measures of disease activity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis

Vogt

Teunissen

Iacobaeus

et al. 2008

Journal of Neurology, Neurosurgery & Psychiatry

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“…Myelin oligodendrocyte glycoprotein (MOG) is a target myelin antigen for both humoral and cellular CNS-directed immune responses. The full-length protein contains 218 aa and two predicted transmembrane domains, is posttranscriptionally processed as suggested by apparent electrophoretic mobility, and is a potential site for glycosylation, phosphorylation, isoprenylation, and myristoylation (4). The encephalitogenic properties of MOG are believed to result from the extracellular location of its IgV-like domain on the outermost myelin lamellae, which makes it an exposed target accessible to initial autoimmune attack on compact myelinated axons (5).…”

Section: Ultiple Sclerosis (Ms) Is An Immune-mediated Chronicmentioning

confidence: 99%

“…Previous studies, either in MS or EAE, have not fully characterized the structural features of the proteins used as Ab targets in vitro and have reported conflicting findings, in part because of the different folded forms of this poorly water-soluble antigen. The existing assays detecting anti-MOG Abs use various MOG preparations, recombinant, native-purified, or in vitro-translated proteins of variable length including short peptides (4,(8)(9)(10)(11). None of these methods takes into account the specific tertiary structure of the folded MOG as it is presented to the immune system in vivo, e.g., in association with a hydrophobic, lipid-rich bilayer membrane environment.…”

Section: Ultiple Sclerosis (Ms) Is An Immune-mediated Chronicmentioning

confidence: 99%

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Lalive

Menge

Delarasse

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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158

113

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Myelin oligodendrocyte glycoprotein (MOG) is an integral membrane protein expressed in CNS oligodendrocytes and outermost myelin lamellae. Anti-MOG Abs cause myelin destruction (demyelination) in animal models of multiple sclerosis (MS); however, such pathogenic Abs have not yet been characterized in humans. Here, a method that specifically detects IgG binding to human MOG in its native, membrane-embedded conformation on MOG-transfected mammalian cells was used to evaluate the significance of these auto Abs. Compared with healthy controls, native MOGspecific IgGs were most frequently found in serum of clinically isolated syndromes (P < 0.001) and relapsing-remitting MS (P < 0.01), only marginally in secondary progressive MS (P < 0.05), and not at all in primary progressive MS. We demonstrate that epitopes exposed in this cell-based assay are different from those exposed on the refolded, extracellular domain of human recombinant MOG tested by solid-phase ELISA. In marmoset monkeys induced to develop MS-like CNS inflammatory demyelination, IgG reactivity against the native membrane-bound MOG is always detected before clinical onset of disease (P < 0.0001), unlike that against other myelin constituents. We conclude that (i) epitopes displayed on native, glycosylated MOG expressed in vivo are early targets for pathogenic Abs; (ii) these Abs, which are not detected in solidphase assays, might be the ones to play a pathogenic role in early MS with predominant inflammatory activity; and (iii) the cell-based assay provides a practical serologic marker for early detection of CNS autoimmune demyelination including its preclinical stage at least in the primate MS model. allergic encephalomyelitis ͉ autoimmunity ͉ clinically isolated syndrome ͉ demyelination

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“…MOG is located on the outer myelin sheath with the N-terminal amino acids 1 to 125 exposed to the extracellular environment where it is accessible for immune cells (Kroepfl et al 1996;Ohler et al 2004). MOG probably forms homodimers (Clements et al 2003) and is highly conserved among species (Delarasse et al 2006;Mesleh et al 2002). The function of MOG in the CNS is unknown, as MOG-deficient mice do not present clinical or histological abnormalities (Delarasse et al 2003).…”

Section: Myelin Oligodendrocyte Glycoproteinmentioning

confidence: 99%

Modelling of Autoimmune Encephalomyelitis in a Non-Human Primate

Jagessar¹,

Heijmans²,

Driel³

et al. 2011

Pathogenesis of Encephalitis

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Marmoset Fine B Cell and T Cell Epitope Specificities Mapped onto a Homology Model of the Extracellular Domain of Human Myelin Oligodendrocyte Glycoprotein

Cited by 23 publications

References 62 publications

Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis

Cerebrospinal fluid anti-myelin antibodies are related to magnetic resonance measures of disease activity in multiple sclerosis

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Modelling of Autoimmune Encephalomyelitis in a Non-Human Primate

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