In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis

Lassmann, Hans; Stemberger, H; Kitz, K.; Wı́sniewski, Henryk M.

doi:10.1016/0022-510x(83)90086-2

Cited by 34 publications

(7 citation statements)

References 24 publications

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“…Thus, the mechanism of tissue injury resembles one postulated to occur in a subset of MS patients. 48 However, this study strongly suggests a direct role of AQP-4 antibodies in causing astrocytopathy, a feature clearly distinguishing NMO from MS. It further suggests that anti-AQP-4 antibodies are modifying factors of NMO, like the anti-MOG and anti-neurofascin antibodies in MS.…”

Section: Fig 6 Aquaporin-4 (Aqp-4) Is Not Targeted By Human Anti-aqpmentioning

confidence: 97%

“…Furthermore, in the CNS, autoantibodies can become pathogenic only in the presence of activated effector cells such as macrophages 47 or of sufficient amounts of complement. 35,48 In vitro studies have shown that NMO Ig is able to lyse rat astrocytes in a complement-dependent manner. 27 All these conditions are fully fulfilled in a T-cell-mediated inflammatory environment in the CNS.…”

Section: Fig 6 Aquaporin-4 (Aqp-4) Is Not Targeted By Human Anti-aqpmentioning

confidence: 99%

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Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Bradl

Misu

Takahashi

et al. 2009

Annals of Neurology

516

500

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Section: Fig 6 Aquaporin-4 (Aqp-4) Is Not Targeted By Human Anti-aqpmentioning

confidence: 97%

Section: Fig 6 Aquaporin-4 (Aqp-4) Is Not Targeted By Human Anti-aqpmentioning

confidence: 99%

Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Bradl

Misu

Takahashi

et al. 2009

Annals of Neurology

516

500

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“…Under normal conditions, the blood–brain barrier restricts entry of serum proteins into the CSF compartment, which makes it unlikely that autoantibody concentrations are reached that are high enough to initiate lesions. Furthermore, in the CNS, autoantibodies can become pathogenic only in the presence of activated effector cells such as macrophages47 or of sufficient amounts of complement 35, 48. In vitro studies have shown that NMO Ig is able to lyse rat astrocytes in a complement‐dependent manner 27.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of follicular variant of papillary thyroid carcinoma in fine-needle aspirates processed by ultrafast Papanicolaou stain

Yang

Liebeskind

Messina

2006

Cancer

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Objective Severe inflammation and astrocyte loss with profound demyelination in spinal cord and optic nerves are typical pathological features of neuromyelitis optica (NMO). A diagnostic hallmark of this disease is the presence of serum autoantibodies against the water channel aquaporin‐4 (AQP‐4) on astrocytes. Methods We induced acute T‐cell–mediated experimental autoimmune encephalomyelitis in Lewis rats and confronted the animals with an additional application of immunoglobulins from AQP‐4 antibody–positive and –negative NMO patients, multiple sclerosis patients, and control subjects. Results The immunoglobulins from AQP‐4 antibody–positive NMO patients are pathogenic. When they reach serum titers in experimental animals comparable with those seen in NMO patients, they augment clinical disease and induce lesions in the central nervous system that are similar in structure and distribution to those seen in NMO patients, consisting of AQP‐4 and astrocyte loss, granulocytic infiltrates, T cells and activated macrophages/microglia cells, and an extensive immunoglobulin and complement deposition on astrocyte processes of the perivascular and superficial glia limitans. AQP‐4 antibody containing NMO immunoglobulin injected into naïve rats, young rats with leaky blood–brain barrier, or after transfer of a nonencephalitogenic T‐cell line did not induce disease or neuropathological alterations in the central nervous system. Absorption of NMO immunoglobulins with AQP‐4–transfected cells, but not with mock‐transfected control cells, reduced the AQP‐4 antibody titers and was associated with a reduction of astrocyte pathology after transfer. Interpretation Human anti–AQP‐4 antibodies are not only important in the diagnosis of NMO but also augment disease and induce NMO‐like lesions in animals with T‐cell–mediated brain inflammation. Ann Neurol 2009;66:630–643

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“…This antibody did not migrate with the oligoclonal bands founds in the same animals, suggesting that the oligoclonal bands may not be of pathogenic importance. Serum from guinea pigs with R-EAE is reported to be able to produce demyelination in central and peripheral nervous tissue in vivo [24,27].…”

Section: Immunopathogenesismentioning

confidence: 99%

Relapsing experimental allergic encephalomyelitis an autoimmune model of multiple sclerosis

Lublin

1985

Springer Semin Immunopathol

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R-EAE is a valuable model for human MS. Table 2 outlines the similarities between R-EAE and MS. The clinical course and pathologic changes seen in this model accurately reflect the pattern of MS. The immunologic changes seen in animals with R-EAE also are similar to those seen in MS. Therefore, the clinicopathologic features of MS can be duplicated with a purely autoimmune model. Although this is of considerable pathogenic significance in understanding MS, we do not know what the inciting event is in MS that would be the equivalent of immunizing an animal with neural antigen. Despite this, R-EAE has and should continue to provide experimental data of considerable importance to an understanding of the mechanisms involved in the evolution of inflammatory demyelination. Other important models of MS utilize viral-induced demyelination. Although the clinical picture of most of the chronic demyelinating viral infections does not show as clear a relapsing or remitting pattern as seen in R-EAE, viral etiologies better fit the epidemiology of MS [16]. Several studies have demonstrated development of an acute EAE-like disease with sensitization to neural antigens following viral infection [12, 30, 56]. Thus, one can hypothesize an initial viral illness causing sensitization of the host to a neural antigen (?MBP) with a subsequent immunopathogenic course similar to that seen in R-EAE. Whether this will in fact be the case remains unproven as yet. Our understanding of the immunopathogenic mechanisms underlying inflammatory demyelination has been enlarged through studies of R-EAE. It is now clear that the minimal myelin antigen necessary for production of the disease is MBP, although this may differ in some species. The relapsing nature of this disorder is mediated in part through lymphocytes, as demonstrated in transfer studies, and thus does not require persistent antigenic depots. There is a genetic susceptibility to development of the CNS autoimmune state, and we speculate that an as yet unidentified perturbation of the host immune system allows for the occurrence of relapsing disease (Table 3).

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In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis

Cited by 34 publications

References 24 publications

Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo

Diagnostic accuracy of follicular variant of papillary thyroid carcinoma in fine-needle aspirates processed by ultrafast Papanicolaou stain

Relapsing experimental allergic encephalomyelitis an autoimmune model of multiple sclerosis

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