Paraneoplastic stiff-person syndrome: passive transfer to rats by means of IgG antibodies to amphiphysin

Sommer, Claudia; Weishaupt, Andreas; Brinkhoff, Jörg; Biko, Lydia; Wessig, Carsten; Gold, Ralf; Toyka, Klaus V.

doi:10.1016/s0140-6736(05)66376-3

Cited by 207 publications

(118 citation statements)

References 23 publications

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“…Exceptions are the neurological syndromes associated with paraneoplastic antibodies that are directed against antigens that are located at the surface of the cell (i.e., antigens that are accessible to circulating antibodies). These include not only disorders of the peripheral nervous system (LEMS, myasthenia gravis, and neuromyotonia) but also antimGluR1-associated PCD and antiamphiphysin-associated stiff-person syndrome [24,25]. Immunotherapy modalities that are recommended for these disorders include plasma exchange, immunoadsorption (extraction of patient IgG over a protein A column), steroids, and i.v.…”

Section: Treatment and Prognosismentioning

confidence: 99%

Managing Paraneoplastic Neurological Disorders

2006

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Section: Treatment and Prognosismentioning

confidence: 99%

Managing Paraneoplastic Neurological Disorders

2006

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“…With regard to immunotherapy, both corticosteroids and immunosuppressants (e. g., cyclophosphamide) can be effective [80,87,88]. Remarkably, experimental data has indicated that anti-amphiphysin-Abs may play a direct pathogenetic role in SPS; up to now, this has not been demonstrated for any other antibody directed against an intracellular antigen [89]. In SPS patients with anti-GAD-Abs, IVIG (2 g/kg per cycle every 4 weeks) was found to be effective and is recommended as first-line therapy [81,90].…”

Section: Stiff-person Syndrome (Sps)mentioning

confidence: 99%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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AbsTR Ac TParaneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. Neurological deficits develop in 2/3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineuronal antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. Highdose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g., during tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of the antineuronal antibodies. Disorders with antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendation is provided along with discussion of currently not validated, but potentially effective new therapies. E264Ayzenberg I et al. Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 course, treatment response and prognosis of PNS [2,3]. Depending on tumor association, obligate and facultative paraneoplastic Abs are differentiated (Tab. 1).Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl. brainstem encephalitis) ▪ Limbic encephalitis ▪ Subacute cerebellar degeneration ▪ Opsoclonus-myoclonus syndrome ▪ Optic neuritis/neuromyelitis optica ▪ Myelopathy/myelitis ▪ Stiff person syndrome ▶Table 1 Paraneoplastic antibodies: associated neurological syndromes and tumors. Target antigen clinical presentation# Association with tumorObligate paraneoplastic Abs (directed against intracellular antigens; tumor association > 95 %) In this review we discuss the diagnosis and management of PNS. With regard to facultative paraneoplastic syndromes which are more frequently of autoimmune origin, such as neuromyelitis optica or myasthenia gravis, the reader should refer to pertinent reviews [5,6]. Diagnostic and Pathogenetic Significance of Antibodies to Intracellular and Surface AntigensAntibodies (Abs) to intracellular antigens or so-called "classical" Abs are almost always tumor-associated (exception: GAD-Abs). They can be associated with various tumors and a variety of neurological conditions [7]. However, a direct pathogenetic significance of these Abs has not yet been demonstrated. Abs to intracellular antigens serve as useful diagnostic markers in the targeted tumor search in PNS. Here, cell-mediated immune responses play a major p...

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“…In various transfer approaches repeated attempts have been made to induce disease symptoms or pathological changes by transfer of patient sera with Hu or Yo antibodies into experimental animals. With some exceptions [40], these studies generally did not show antibody-induced cell death [41][42][43][44]. Probably one of the reasons for this failure to induce cell death after transfer or injection of antibodies into the brain is that, even if they reach the targeted neurons, the antibodies cannot enter the cytoplasm of these intact cells.…”

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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Paraneoplastic stiff-person syndrome: passive transfer to rats by means of IgG antibodies to amphiphysin

Cited by 207 publications

References 23 publications

Managing Paraneoplastic Neurological Disorders

Managing Paraneoplastic Neurological Disorders

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Autoimmune Epilepsies

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