Autoantikörper gegen ganglionäre Azetylcholinrezeptoren und autoimmune autonome Gangliopathie

Zusammenfassung

Nikotinische Azetylcholinrezeptoren sind ligandengesteuerte Kationenkanäle, die in allen Bereichen des Nervensystems vorkommen. Autoantikörper gegen die ╒3-Untereinheit ganglionärer nikotinischer Azetylcholinrezeptoren (nAChR) werden bei etwa 50% der Patienten mit autoimmuner autonomer Gangliopathie (AAG) angetroffen. Die Autoantikörper sind wie bei der Myasthenia gravis die eigentlichen Verursacher der autonomen Störungen. Ihre Konzentration im Blut korreliert mit dem Schweregrad der autonomen Symptome, eine Reduktion der Antikörperkonzentration durch Plasmaaustausch oder Immunsuppressiva führt zu einer deutlichen Besserung der klinischen Symptome. Die AAG erfüllt die Kriterien einer echten Autoimmunerkrankung. Sie kann durch aktive und passive Immunisierung im Tiermodell imitiert werden. Die menschlichen und bei Tieren induzierten Antikörper hemmen dosisabhängig die Signalübertragung ganglionärer nAChR in rezeptortragenden Kulturzellen. Unklar ist noch, welche Faktoren die unterschiedliche Ausprägung der autonomen Symptome beeinflussen und ob eine unterschiedliche Feinspezifität der Autoantikörper oder zusätzliche Autoantikörper gegen weitere Untereinheiten der ganglionären nAChR für das Erscheinungsbild der Erkrankungen von Bedeutung sind.

Summary

Nicotinic acetylcholine receptors (nAChR) are ligand-gated cation channels that are present throughout the nervous system. Antibodies against the ╒3-subunit of ganglionic nicotinic acetylcholine receptors are found in about 50% of patients suffering from an autoimmune autonomic gangliopathy (AAG). The serum levels of AChR-binding antibodies correlate with the severity of autonomic failure and a reduction of antibodies in the serum by means of plasma exchange or immunosuppression is followed by improvement in autonomic function. An animal model of the disease can be induced by active immunization of rabbits with ganglionic AChR and by passive administration of rabbit and human antibodies into mice. The antibodies inhibit in a dose-dependent manner the signal transfer of ganglionic AChR in neuroblastoma cells. It is unclear, which factors regulate the expression of different autonomic symptoms of the disease in patients and if other unknown antibodies against ganglionic receptors or antibodies against other structures engaged in autonomic signal transduction are also involved in different subgroups of the disease.

Schlüsselwörter

Autoimmunität - Gangliopathie - autonome Neuropathie - Dysautonomie - Azetylcholinrezeptorantikörper

Keywords

Autoimmunity - gangliopathy - autonomous neuropathy - dysautonomia - acetylcholine receptor antibody

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