Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event

Berger, Thomas; Rubner, P.; Schautzer, Franz; Egg, R.; Ulmer, Hanno; Mayringer, Irmgard; Dilitz, Erika; Deisenhammer, Florian; Reindl, Markus

doi:10.1056/nejmoa022328

Cited by 585 publications

(387 citation statements)

References 33 publications

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“…Although MS is primarily mediated by autoreactive T cells, the majority of biomarker candidates have resulted from studies of humoral immunity or biochemical serum parameters (Berger et al 2003, Amorini et al 2009). Nonetheless, a reliable indication of specific antibodies has not been shown to promote an earlier diagnosis of MS in patients (Lim et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Seger¹,

Zorzella-Pezavento²,

Pelizon³

et al. 2010

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 99%

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Seger¹,

Zorzella-Pezavento²,

Pelizon³

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…Reports of enhanced MOG-specific T cell (25)(26)(27)(28) and Ab (28 -31) responses in MS patients suggest that autoimmunity to MOG may play a similar role in the pathogenesis of human disease. This concept is supported by the demonstration of MOG-reactive Abs associated with disintegrating vesicular myelin debris in acute demyelinating MS lesions (22,32) and a recent report that MOG-specific Ab can be used as a prognostic marker early in the course of disease (33).…”

mentioning

confidence: 81%

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

119

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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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“…Antimyelin component antibodies generated under pathological conditions might have either adverse or beneficial effects (van der Veen et al, 1986(van der Veen et al, , 1989Endoh et al, 1986;Sadler et al, 1991;Potter and Stephens, 1994;Genain et al, 1995;Laman et al, 2001;Morris-Downes et al, 2002;Mitsunaga et al, 2002;Schwab, 2004). Moreover, potential pathogenetic roles for antimyelin antibodies, including anti-PLP antibodies, have been suggested in MS (Sun et al, 1991;Warren et al, 1994;Sellebjerg et al, 1995Sellebjerg et al, , 2000Archelos et al, 2000;Carvalho et al, 2003;Berger et al, 2003;Qin et al, 2003;Kanter et al, 2005;Zhang et al, 2005a). Furthermore, recent studies implicate an autoantibody to nonmyelinating cell populations in the pathogenesis of the MS variant neuromyelitis optica (Lennon et al, 2005) and specific antibody localization on axons in MS plaques (Zhang et al, 2005b).…”

Section: Implications For Msmentioning

confidence: 99%

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

Greenfield¹,

Reddy²,

Lees³

et al. 2006

J of Neuroscience Research

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Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti‐100–123 mAb did not recognize DM‐20, the PLP isoform that lacks residues 116–150. All of the mAbs stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS myelin despite greater diversity of their pgf myelin protein sequences. Myelin staining was observed when there was at least 40% identity of the mAb epitope and known pgf myelin proteins of the same or related species. The pgf myelin proteins of teleosts and elasmobranchs lack 116–150; the anti‐100–123 mAb did not stain their myelin. In addition to myelin, the anti‐178–191 mAb stained many neurons in all species; other mAbs stained distinct neuron subpopulations in different species. Neuronal staining was observed when there was at least approximately 30% identity of the PLP mAb epitope and known pgf neuronal proteins of the same or related species. Thus, anti‐human PLP epitope mAbs simultaneously recognize CNS myelin and neurons even without extensive sequence identity. Widespread anti‐PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti‐PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions. © 2006 Wiley‐Liss, Inc.

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Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event

Cited by 585 publications

References 33 publications

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

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

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

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