Neurology · 2015
Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons.
Клинический случайСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Piepgras Johannes, Höltje Markus, Michel Klaus, Li Qin, Otto Carolin, Drenckhahn Christoph, Probst Christian, Schemann Michael, Jarius Sven, Stöcker Winfried, Balint Bettina, Meinck Hans-Michael, Buchert Ralph, Dalmau Josep, Ahnert-Hilger Gudrun, Ruprecht Klemens
Аннотация
OBJECTIVE: To characterize pathogenic effects of antibodies to dipeptidyl-peptidase-like protein 6 (DPPX), a subunit of Kv4.2 potassium channels, on gut and brain neurons.
METHODS: We identified a new patient with anti-DPPX encephalitis and analyzed the effects of the patient's serum and purified immunoglobulin G (IgG), and of serum of a previous patient with anti-DPPX encephalitis, on the activity of enteric neurons by voltage-sensitive dye imaging in guinea pig myenteric and human submucous plexus preparations. We studied the subcellular localization of DPPX by immunocytochemistry in cultured murine hippocampal neurons using sera of 4 patients with anti-DPPX encephalitis. We investigated the influence of anti-DPPX-containing serum and purified IgG on neuronal surface expression of DPPX and Kv4.2 by immunoblots of purified murine hippocampal neuron membranes.
RESULTS: The new patient with anti-DPPX encephalitis presented with a 2-month episode of diarrhea, which was followed by tremor, disorientation, and mild memory impairment. Anti-DPPX-IgG-containing sera and purified IgG increased the excitability and action potential frequency of guinea pig and human enteric nervous system neurons. Patient sera revealed a somatodendritic and perisynaptic neuronal surface staining that colocalized with the signal of commercial anti-DPPX and Kv4.2 antibodies. Incubation of hippocampal neurons with patient serum and purified IgG resulted in a decreased expression of DPPX and Kv4.2 in neuronal membranes.
CONCLUSIONS: Hyperexcitability of enteric nervous system neurons and downregulation of DPPX and Kv4.2 from hippocampal neuron membranes mirror the clinical phenotype of patients with anti-DPPX encephalitis and support a pathogenic role of anti-DPPX antibodies in anti-DPPX encephalitis.
METHODS: We identified a new patient with anti-DPPX encephalitis and analyzed the effects of the patient's serum and purified immunoglobulin G (IgG), and of serum of a previous patient with anti-DPPX encephalitis, on the activity of enteric neurons by voltage-sensitive dye imaging in guinea pig myenteric and human submucous plexus preparations. We studied the subcellular localization of DPPX by immunocytochemistry in cultured murine hippocampal neurons using sera of 4 patients with anti-DPPX encephalitis. We investigated the influence of anti-DPPX-containing serum and purified IgG on neuronal surface expression of DPPX and Kv4.2 by immunoblots of purified murine hippocampal neuron membranes.
RESULTS: The new patient with anti-DPPX encephalitis presented with a 2-month episode of diarrhea, which was followed by tremor, disorientation, and mild memory impairment. Anti-DPPX-IgG-containing sera and purified IgG increased the excitability and action potential frequency of guinea pig and human enteric nervous system neurons. Patient sera revealed a somatodendritic and perisynaptic neuronal surface staining that colocalized with the signal of commercial anti-DPPX and Kv4.2 antibodies. Incubation of hippocampal neurons with patient serum and purified IgG resulted in a decreased expression of DPPX and Kv4.2 in neuronal membranes.
CONCLUSIONS: Hyperexcitability of enteric nervous system neurons and downregulation of DPPX and Kv4.2 from hippocampal neuron membranes mirror the clinical phenotype of patients with anti-DPPX encephalitis and support a pathogenic role of anti-DPPX antibodies in anti-DPPX encephalitis.