Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis

Bernal, Fabián; Graus, Francesc; Pifarré, Alex; Sáiz, Albert; Benyahia, B.; Ribalta, Teresa

doi:10.1007/s00401-001-0498-0

Cited by 159 publications

(93 citation statements)

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“…The participation of both cellular and humoral immunity has been demonstrated in several immune-mediated diseases [3,16,19]. In human idiopathic SN, both T cell-mediated immune response and autoantibody against spinal ganglion neurons were involved on its pathogenesis [1,9,16,18]. However, a previous report of human acute SN [10] described that CD8 positive-T cell-mediated immunity against ganglion neurons might mostly contribute the pathologic events and humoral immunity had only a limited role.…”

Section: Discussionmentioning

confidence: 99%

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

Funamoto

Nibe

Morozumi

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Canine ganglioradiculitis (sensory neuropathy) was examined pathologically in two dogs (dog Nos. 1 and 2). The affected dogs had 1 and 2 years clinical courses from the onset, respectively. As common clinical signs, both cases showed progressive ataxia, difficulty in prehending food, visual deficit, and several sensory abnormalities. Gross observation after tissue fixation revealed whitish discoloration in the dorsal column of the spinal cords. The histological lesions were mainly distributed in the spinal dorsal roots, ganglions, and dorsal columns. In the spinal dorsal roots and ganglions, there were striking myelin loss, mild infiltration of mononuclear cells, and proliferation of small spindle cells. In the dorsal funiculus, there were moderate to severe diffuse myelin-loss and axonal degeneration. Immunohistochemistry for substance P (SP) revealed marked reduction of SP-immunopositive granules in the spinal substantia gelatinosa of affected dogs. By immunohistochemistry, CD3-positive cells were observed in the dorsal roots of dog No. 2, while CD3-positive cells were rare in those of dog No. 1. In the spinal ganglion of dog No. 1 there were many CD3-and MHC class II-positive cells. By indirect immunofluorescence assay using sera from affected dogs, no autoantibodies against canine nerve tissues were detected. The clinicopathological features of the present cases are almost consistent with those in previous reports of canine sensory neuropathies, while the etiology remains unclear.

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Section: Discussionmentioning

confidence: 99%

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

Funamoto

Nibe

Morozumi

et al. 2007

The Journal of Veterinary Medical Science

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“…A 1:1 ratio of T cells-neurons is sufficient for toxicity to manifest. This ratio is achievable in vivo because many T cells are known to cluster around neurons in neuroinflammatory diseases of humans and experimental models (41,42).…”

Section: Discussionmentioning

confidence: 99%

Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity

Giuliani

Goodyer

Antel

et al. 2003

The Journal of Immunology

199

145

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Axonal and neuronal loss occurs in inflammatory diseases of the CNS such as multiple sclerosis. The cause of the loss remains unclear. We report that polyclonally activated T cells align along axons and soma of cultured human neurons leading to substantial neuronal death. This occurs in an allogeneic and syngeneic manner in the absence of added Ag, requires T cells to be activated, and is mediated through cell contact-dependent mechanisms involving FasL, LFA-1, and CD40 but not MHC class I. Activated CD4+ and CD8+ T cell subsets are equally neuronal cytotoxic. In contrast to neurons, other CNS cell types (oligodendrocytes and astrocytes) are not killed by T cells. These results demonstrate for the first time the high and selective vulnerability of human neurons to T cells, and suggest that when enough activated T cells accumulate in the CNS, neuronal cytotoxicity can result through Ag-independent non-MHC class I mechanisms.

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“…Detailed immunopathological studies of biopsies and autopsies of such brains provide a good explanation for this. In specimens from patients with onconeural antibodies, an intense T-cell-mediated inflammation with clear evidence of a cytotoxic T-cell response via the perforin-granzyme B pathway has been found [27,45].…”

Section: Studies With Antibodies Against Intracellular Antigensmentioning

confidence: 99%

Autoimmune Epilepsies

Bien

Bauer

2014

Neurotherapeutics

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In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody-and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.

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Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis

Cited by 159 publications

References 0 publications

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity

Autoimmune Epilepsies

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