Endoneurial injection of antisera to myelin antigens

Hughes, Richard; Powell, Henry C.; Braheny, Sherry L.; Brostoff, Steven W.

doi:10.1002/mus.880080607

Cited by 36 publications

(15 citation statements)

References 20 publications

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“…to avoid this issue. The inflammation and demyelination found in the control rats injected with PBS was not unexpected, as previous studies have shown 16 . It is well known that nervous tissue trauma provokes or enhances myelin antigen autoreactive T‐ and B‐cell responses 17 and may provoke immunopathological events 18 .…”

Section: Discussionsupporting

confidence: 53%

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Local effects of recombinant rat interleukin‐6 on the peripheral nervous system

et al. 1999

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Interleukin-6 (IL-6) is a multifunctional cytokine with a broad range of activities and can affect a variety of target cells or systems in multiple ways. However, there is currently no consensus on how IL-6 directly affects the peripheral nervous tissue. We performed histopathological and immunohistochemical analyses to investigate the direct effects of recombinant rat IL-6 (rrIL-6) following its intraneural injection into the sciatic nerve of adult Lewis rats. One day after injection, a large number of macrophages, major histocompatibility complex (MHC) class II positive cells, and CD4+ and CD8+ T cells appeared within the perineurium and endoneurium. From day 4 to day 7 after injection, we observed a gradual increase of inflammation and demyelination. On day 7, demyelination affected more than 80% of nerve fibres. In contrast, in the sterile phosphate-buffered saline (PBS)-injected control group, lower inflammation and fewer demyelinating nerve fibres were observed on days 4 and 7. Thus, intraneural injection of rrIL-6 into the sciatic nerve induces high inflammation and severe demyelination. This study improves our understanding of the effector mechanisms underlying inflammation and demyelination and identifies IL-6 as an essential mediator of inflammation and demyelination in the peripheral nervous system after local administration.

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Section: Discussionsupporting

confidence: 53%

“…Therefore we followed many of the recommendations of Dyck et al 14 . and Hugues et al 16 . to avoid this issue.…”

Section: Discussionmentioning

confidence: 99%

Local effects of recombinant rat interleukin‐6 on the peripheral nervous system

et al. 1999

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“…We therefore cannot exclude the possibility that they are the consequence rather than the cause of the disease, a criticism that could be levelled at the evidence for many auto-immune diseases. The experimental observation that experimental and human anti-P0 antibodies induce demyelination following intraneural injection lends support to the hypothesis that they play a part in pathogenesis (Hughes et al, 1985;Yan et al, 2001).…”

Section: Characteristics Of Patients With Antibodiesmentioning

confidence: 68%

Antibodies to peripheral nerve myelin proteins in chronic inflammatory demyelinating polyradiculoneuropathy

Allen

Γιαννόπουλος

Gray

et al. 2005

J Peripheral Nervous Sys

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disorder of the peripheral nervous system with a probable auto-immune pathogenesis. The nature of the responsible autoantigens is unclear in most patients. We used the Western immunoblot technique to seek antibodies to peripheral nerve protein antigens. Sera from eight of 32 (25%) CIDP patients, 12 of 37 (32%) Guillain-Barré syndrome (GBS) patients, zero of 30 (0%) chronic idiopathic axonal polyneuropathy patients and two of 39 (5%) healthy control subjects contained anti-peripheral nerve protein antibodies. The frequency of such antibodies was significantly greater in both CIDP (p = 0.04) and GBS (p = 0.003) patients than in normal control subjects. For CIDP patients, there were non-significant trends for antibodies to be more common in females and in those who responded to treatment with either intravenous immunoglobulin or plasma exchange. The commonest antibodies were directed against a band at 28 kDa, resembling that labelled by a monoclonal antibody against myelin protein zero (P0). Six CIDP and seven GBS patients' sera reacted with this band. These results support the view that antibodies to myelin proteins, and especially P0, are present in the serum of some patients with CIDP and GBS.

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“…Administration of antibodies alone does not induce disease, probably because they do not reach the endoneurium. Intraneural injection of antibodies directed against myelin antigens, especially those such as galactocerebroside and P0 which are abundantly expressed at the myelin–Schwann cell surface, induces demyelination ( Hughes et al, 1985 ) . The models most studied have been acute, with disease developing after about 10 days, reaching a nadir after about 15 days and recovering substantially by 28 days.…”

Section: Experimental Modelsmentioning

confidence: 99%

“…With the possible exception of P0, there is no convincing evidence of antibodies to myelin proteins being formed in CIDP. By contrast, antibodies to proteins such as P0 which are expressed at the myelin–Schwann cell surface do cause demyelination upon intraneural injection ( Hughes et al, 1985 ) and remain possible agents of demyelination in CIDP. The detection of antibodies to P0 and other myelin protein antigens is likely to be critically dependent on the conformation of the antigen which may only be realized on the intact protein in its usual membrane environment.…”

Section: Antibodiesmentioning

confidence: 99%

Pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy

Hughes

Allen

Makowska

et al. 2006

J Peripheral Nervous Sys

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142

104

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The acute lesions of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of endoneurial foci of chemokine and chemokine receptor expression and T cell and macrophage activation. The myelin protein antigens, P2, P0, and PMP22, each induce experimental autoimmune neuritis in rodent models and might be autoantigens in CIDP. The strongest evidence incriminates P0, to which antibodies have been found in 20% of cases. Failure of regulatory T-cell mechanism is thought to underlie persistent or recurrent disease, differentiating CIDP from the acute inflammatory demyelinating polyradiculoneuropathy form of Guillain-Barré syndrome. Corticosteroids, intravenous immunoglobulin and plasma exchange each provide short term benefit but the possible long-term benefits of immunosuppressive drugs have yet to be confirmed in randomised, controlled trials.

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Endoneurial injection of antisera to myelin antigens

Cited by 36 publications

References 20 publications

Local effects of recombinant rat interleukin‐6 on the peripheral nervous system

Local effects of recombinant rat interleukin‐6 on the peripheral nervous system

Antibodies to peripheral nerve myelin proteins in chronic inflammatory demyelinating polyradiculoneuropathy

Pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy

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