Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis

Menge, Til; Lalive, Patrice H.; Büdingen, Hans‐Christian von; Cree, Bruce; Genain, Claude P.

doi:10.1016/j.jaci.2005.03.023

Cited by 69 publications

(43 citation statements)

References 36 publications

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“…To consolidate this contention, the hMOG cme assay was used to study the time course of the Ab response against hMOG cme in marmoset EAE induced by immunization with human white matter. In these animals, serum reactivity against hMOG cme was always detected before clinical onset, contrary to anti-myelin basic protein and antigalactocerebroside Abs that occur at later stages (21). Because the immunizing antigen contained native MOG similar in conformation to hMOG cme , these findings imply that the hMOG cme -reactive Abs are the ones that initiate and͞or first result from active demyelination.…”

Section: Discussionmentioning

confidence: 78%

“…The high prevalence of hMOG cme -reactive Abs in CIS, i.e., contemporary of the first clinically apparent event for MS, is in sharp contrast to other antimyelin Abs, such as those directed against glycolipids that predominate in established MS (21). This observation has two important implications: first, it suggests that hMOG cme -reactive Abs may be implicated in the early pathogenesis of disease.…”

Section: Discussionmentioning

confidence: 98%

“…20). Abs against galactocerebroside, the major myelin glycolipid, are not found in PPMS but are associated mostly with established relapsing-remitting and secondaryprogressive forms (21). It is thus becoming increasingly apparent that Ab responses against myelin antigens may follow patterns that reflect a combination of underlying cause, antigen exposure, and secondary immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…Further studies are needed to validate this biomarker and understand the benefits and information that in combination with other Ab profiling techniques (8,21) it could provide to scientists, treating neurologists, and individuals with suspected or established MS.…”

Section: Discussionmentioning

confidence: 99%

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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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159

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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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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.

Self Cite

159

113

View full text Add to dashboard Cite

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“…However, the identification of these common loci did not lead immediately to an understanding as to why the central nervous system (CNS) is the primary target of autoimmune injury in MS. Nevertheless, several identified genes are expressed in the CNS, and some, such as GALC, were previously implicated in MS (Menge et al, 2005).…”

Section: Genome-wide Association Screenmentioning

confidence: 99%

Multiple sclerosis genetics

Cree

2014

Handbook of Clinical Neurology

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Quantified CSF antibody reactivity against myelin in multiple sclerosis

Sun

Bakhti

Fitzner

et al. 2015

Ann Clin Transl Neurol

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BackgroundSynthesis of clonal IgG is a consistent feature of patients with multiple sclerosis (MS). Whether oligoclonal bands (OCBs) represent unspecific disease bystanders or active components in MS pathology is an open question. The aim of this study was to develop a method to quantify and compare the reactivity of cerebrospinal fluid (CSF) antibodies from patients with and without MS.MethodsWe collected CSF from 262 patients from two different cohorts, which included 148 patients with MS and 114 with other neurological diseases (OND). We established a highly sensitive electrochemiluminescence (ECL)‐based assay to measure CSF antibody reactivity against purified myelin particles and biotin anchored liposomes. The diagnostic value of the ECL score against myelin particles was assessed with receiver operating characteristic curves.Results CSF from patients with MS have higher reactivity toward purified myelin particles as compared to those with OND with OCBs. Using liposomes with defined lipid compositions and myelin particles from ceramide synthase 2 (CerS2) knockout mice, we find that some of the CSF antibody reactivity is directed against cerebrosides.ConclusionThe ECL‐based assay system expands the currently available toolbox for the detection of autoantibodies in MS and related diseases.

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Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis

Cited by 69 publications

References 36 publications

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

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

Multiple sclerosis genetics

Quantified CSF antibody reactivity against myelin in multiple sclerosis

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