Serum antibodies to neurofilament antigens in patients with neurological and other diseases and in healthy controls

Bahmanyar, Sina; Moreau-Dubois, M C; Brown, Paul; Cathala, F; Gajdusek, D. Carleton

doi:10.1016/0165-5728(83)90009-7

Cited by 69 publications

(19 citation statements)

References 12 publications

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“…The increased incidence of serum immunoreactivity with neurofilament proteins in kuru and Creutzfeldt-Jakob disease compared to healthy controls confirms the results of immunofluorescence studies previously reported from our laboratory (1)(2)(3)(4)(5). There is also an increased incidence of serum reactivity with neurofilament proteins in Alzheimer The incidence of serum immunoreactivity against neurofilament proteins is high not only in Guamanians with amyotrophic lateral sclerosis and with parkinsonism-dementia but also in a control group of Guamanians.…”

Section: Discussionsupporting

confidence: 80%

“…In the work reported here, the specific subunit proteins of neurofilaments to which individual sera containing autoantibodies to neurofilaments react (1)(2)(3)(4)(5)(6)(7) were identified, and the patterns of binding of serum IgG to immunoblots of the specific protein autoantigens in myelinated axons and neurofilament-enriched preparations from mouse brain were studied. The patterns of reactivity of individual sera to the 200-, 150-, and 70-kDa protein components of neurofilaments were studied in 65 sera from patients with subacute spongiform virus encephalopathies (29 kuru, 36 Creutzfeldt-Jakob disease), 79 sera from patients with other neurologic diseases, and 65 sera from normal control subjects.…”

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confidence: 99%

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The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Toh¹,

Gibbs²,

Gajdusek³

et al. 1985

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

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Sera from 65 patients with spongiform virus encephalopathies (29 with kuru, 36 with Creutzfeldt-Jakob disease), 79 with other neurologic diseases, and 65 control subjects were examined for reactivity in immunoblots of preparations of myelinated axons and neuroframents from mouse brain. The sera reacted most frequently with the 200-kDa and 150-kDa neurofilament proteins and less frequently with the 70-kDa neurofilament protein and a 62-kDa neurofilament-associated protein. The sera reacted with the same proteins as those which reacted with rabbit and mouse polyclonal antibodies and mouse monoclonal antibody to neuroframent proteins. Serum reactions were also seen with Trixon X-100 extracts of chimpanzee brain and bovine spinal cord but not with Triton extracts of liver, kidney, and muscle.In the work reported here, the specific subunit proteins of neurofilaments to which individual sera containing autoantibodies to neurofilaments react (1-7) were identified, and the patterns of binding of serum IgG to immunoblots of the specific protein autoantigens in myelinated axons and neurofilament-enriched preparations from mouse brain were studied. The patterns of reactivity of individual sera to the 200-, 150-, and 70-kDa protein components of neurofilaments were studied in 65 sera from patients with subacute spongiform virus encephalopathies (29 kuru, 36 Creutzfeldt-Jakob disease), 79 sera from patients with other neurologic diseases, and 65 sera from normal control subjects. Most positive sera reacted with the 200-kDa component; positive sera reacted next most frequently with the 150-kDa component and infrequently with the 70-kDa protein. A 62-kDa protein which may be a component of neurofilaments was also only rarely reactive. Individual patterns ofreactivity were found in some sera that reacted mainly with the 150-, 70-, and 62-kDa components.Bahmanyar et al. (6) have shown recently that the autoantibody that developed in one chimpanzee infected with Creutzfeldt-Jakob disease reacted principally with the 200-kDa component of neurofilaments but only weakly with the 150-kDa component and not at all with the 70-kDa protein of the triad which comprise neurofilaments.Specificity of the serum reaction for axonal neurofilaments, previously demonstrated by using cultured neurons as subtrate (1, 2), was further supported by the nonreactivity of the sera for other axonal proteins in the immunoblots and by the identical reactivity obtained with heterologous rabbit and mouse polyclonal and mouse monoclonal antibodies to neurofilament proteins. and other axonal proteins, were prepared by the axon-floatation method described in detail elsewhere (8). Whole brains were homogenized in 0.85 M sucrose/30 mM KCl/mM EDTA/20 mM sodium phosphate, pH 6.5, and the axons were recovered as a floating pad after centrifugation for 15 min at 12,000 x g. Neurofilament-enriched preparations were made by extracting whole brain with a Triton X-100 solution, leaving behind Triton-insoluble proteins including those of the neurofilament triplet...

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Toh¹,

Gibbs²,

Gajdusek³

et al. 1985

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

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“…spleen or blood) neuroantigen-specific immune response was not correlated to EAE onset or severity, the results suggest that CSPs may be more sensitive biomarkers for inflammatory demyelinating CNS disease than inflammatory biomarkers such as cytokines. Moreover, CSPs are also expected to be more specific biomarkers for early detection of EAE because they are not expected at appreciable levels in healthy controls, whereas neuroantigen-specific immune responses can be detected in healthy individuals3738.…”

Section: Resultsmentioning

confidence: 99%

Microwave & Magnetic (M2) Proteomics Reveals CNS-Specific Protein Expression Waves that Precede Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

Raphael

Mahesula

Purkar

et al. 2014

Sci Rep

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Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave & magnetic (M2) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M2 proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M2 proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M2 proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.

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“…The degradation of NF in transected rat sciatic nerve is reduced if the influx of calcium into the axoplasm is prevented or if calciumactivated neutral proteases activities are inhibited [155]. Such enzymatic fragmentation in transected nerves generates protease-resistant NF fragments which may represent, after externalisation into the endoneurium, a mechanism responsible for the generation of auto-antibodies to NF proteins detected in Parkinson's disease and in several neurological diseases [184][185][186][187].…”

Section: Degradation Of Neurofilamentsmentioning

confidence: 99%

Review of the Multiple Aspects of Neurofilament Functions, and their Possible Contribution to Neurodegeneration

et al. 2008

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Neurofilaments (NF) are the most abundant cytoskeletal component of large myelinated axons from adult central and peripheral nervous system. Here, we provide an overview of the complementary approaches, including biochemistry, cell biology and transgenic technology that were used to investigate the assembly, axonal transport and functions of NF in normal and pathological situations. Following their synthesis and assembly in the cell body, NFs are transported along the axon. This process is finely regulated via phosphorylation of the carboxy-terminal part of the two high-molecular-weight subunits of NF. The correct formation of an axonal network of NF is crucial for the establishment and maintenance of axonal calibre and consequently for the optimisation of conduction velocity. The frequent disorganisation of NF network observed in several neuropathologies support their contribution. However, despite the presence of NF mutations found in some patients, the exact relations between these mutations, the abnormal NF organisation and the pathological process remain a challenging field of investigation.

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Serum antibodies to neurofilament antigens in patients with neurological and other diseases and in healthy controls

Cited by 69 publications

References 12 publications

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Microwave & Magnetic (M2) Proteomics Reveals CNS-Specific Protein Expression Waves that Precede Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

Review of the Multiple Aspects of Neurofilament Functions, and their Possible Contribution to Neurodegeneration

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