Elevated Levels of Antibody to Myelin Oligodendrocyte Glycoprotein Is Not Specific for Patients With Multiple Sclerosis

Karni, Arnon; Bakimer-Kleiner, Ronit; Abramsky, Oded; Ben‐Nun, Avraham

doi:10.1001/archneur.56.3.311

Cited by 90 publications

(42 citation statements)

References 29 publications

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“…Antibodies produced by cePC do not react with "the usual suspects" MOG and MBP represent encephalitogenic antigens in various animal models of MS and immune responses against these myelin proteins have been detected in the serum and CSF of MS patients [8][9][10][11][12][13][14][15]. No reactivity with these two myelin antigens could be detected by ELISA in the CSF of all four patients (not shown).…”

Section: F) (B-i) Confocal Micrographs Of Immunofluorescence Staininmentioning

confidence: 99%

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Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

et al. 2008

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Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation.

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Section: F) (B-i) Confocal Micrographs Of Immunofluorescence Staininmentioning

confidence: 99%

“…Antibody responses against MOG and other myelin proteins (e.g. myelin basic protein, MBP) have been detected in the serum and CSF of MS patients, but also control subjects [8][9][10][11][12][13][14][15], and their immunopathological significance and usefulness as diagnostic or prognostic marker remain heavily disputed.…”

Section: Introductionmentioning

confidence: 99%

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

et al. 2008

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“…P, Primary progressive; RR, relapsing-remitting; SCP, secondary chronic progressive. The response to the homologous MOG peptide is given in parentheses below the OD obtained for the BTN peptides (29).…”

Section: Discussionmentioning

confidence: 99%

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

Guggenmos

Schubart

Ogg

et al. 2004

The Journal of Immunology

116

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The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76–100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG76–100 in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76–100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1–39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

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“…No MOG-labeled plasma cells were found in brain, although others have reported sequestration of MOG-specific B-cells in brain (62). However, other studies did not find a significantly higher prevalence or level of anti-MOG antibody in CSF of MS patients compared to patients with other neurologic diseases (53,63). A recent attempt to attribute the demyelinating activity in MS patients to anti-MOG antibodies, by linking particular MOG epitopes to MS that are associated with demyelination in EAE, revealed such specificities in the serum from only 1 of 17 MS patients (64).…”

Section: Myelin/oligodendrocyte Glycoprotein (Mog)-mog Is a Strongly mentioning

confidence: 92%

B cells in multiple sclerosis

Mark¹

2004

Front Biosci

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The most common laboratory abnormality in multiple sclerosis (MS) is an increased amount of cerebrospinal fluid IgG and the presence of oligoclonal bands. Despite studies of the humoral response that suggest the involvement of an infectious agent or autoantigen in disease, the major targets of the oligoclonal response are still unknown. Identification of these targets will reveal valuable insights into the cause and pathogenesis of MS and is likely to lead to effective treatment.

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Elevated Levels of Antibody to Myelin Oligodendrocyte Glycoprotein Is Not Specific for Patients With Multiple Sclerosis

Cited by 90 publications

References 29 publications

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

B cells in multiple sclerosis

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